bluuebunny/crossref_metadata_2025 huggingface dataset:
Nicotinic Receptors, Smoking and Schizophrenia
Authors: Leonard Sherry , Gault Judith , Adams Catherine , Breese Charles R. , Rollins Yvonne , Adler Lawrence E. , Olincy Ann , Freedman Robert
Published: December 2024

Neuronal nicotinic acetylcholine receptor expresssion was examined in schizophrenia. The incidence of smoking in schizophrenia is remarkably high and nicotine has been found to normalize an auditory evoked potential deficit seen in most subjects who suffer from this disease. Antagonists and agonists of a specific subset of this receptor family, the a7 nicotinic receptor, were found to regulate the gating of filtering of auditory information in both humans and in an animal model. The a7 gene has been cloned and a polymorphic dinucleotide repeat near the gene was used for linkage analysis, showing the a7 locus to be linked to the P50 deficit. Expression of the a7 receptor, which binds nicotine with low affinity, is reduced in the hippocampus of schizophrenics. [3H]-nicotine binding, a measure of the high affinity nicotinic receptors, was also decreased in schizophrenics and does not increase in response to tobacco use, as is seen in control subjects. The results of these studies suggest the presence of abnormal expression and function of the neuronal nicotinic receptor gene family in schizophrenia.
Identification of Respiratory Neurons Regenerating Axons into	Peripheral Nerve Grafts in Adult Rats
Authors: Kohama Ikuhide , Aoki Mamoru
Published: December 2024

The present aimed to identify the origin of medullary and upper cervical respiratory neurons regenerating their axons into the peripheral nerve grafts in adult rats. We employed an antidromic activation technique and a retrograde horseradish peroxidase (HRP) tracing method for determining the origins of the regenerating axons. Autologous segments of the common peroneal nerve were successfully implanted ventrolaterally into the proximal cut end of the C2 spinal cord hemisection (n = 24). Two to 5 months after implantation, spontaneous multi-unit discharges were recorded in all grafts; respiratory-related discharges in 21 (87.5%) grafts; and non-respiratory discharges in 3 (12.5%) grafts. The respiratory discharge patterns were similar to those for normal respiratory efferent neurons in rats. After the recordings were completed, 5 of 182 respiratory units explored in the medullary ventral respiratory cell group (VRG) neurons were antidromically activated by electrical stimulation of the grafts (n = 15). The estimated axonal conduction velocities ranged from 5.6 to 7.4 (mean 6.7) m/s. Retrograde horseradish peroxidase (HRP) labelings applied to the distal cut end of the grafts (n = 13) revealed that HRP-labeled cells were located, predominantly ipsilaterally, in the brainstem up to 5-10 mm distant from the implanted site. Some HRP-labeled cells were observed in the region of the nucleus ambiguus where many respiratory neurons exist. These results demonstrate that peripheral nerve grafts implanted in the C2 segment can induce axonal regeneration of medullary VRG neurons conveying funcional efferent signals.
Tolerance to and Dependence on Alprazolam are Due to Changes in	GABAa Receptor Function and Are Independent of Exposure to Experimental	Set-up
Authors: Galici Ruggero , Pinna Graziano , Stephens David N. , Schneider Herbert H. , Turski Lechoslaw
Published: December 2024

The development of tolerance to and dependence on BDZs was investigated by monitoring locomotor activity in mice. Alprazolam (6 mg/kg twice daily s.c.) or solvent were administered over 12 days. The treatment schedule at least 50% BDZ receptor occupancy throughout treatment. Receptor occupancy half-lives were determined to be 2.6 hrs and 4.8 hrs. after cessation of 4 and 12 days of alprazolam administration, respectively. To assess if the tolerance to and dependence on alprazolam were due to repeated exposure of mice to the experimental set-up, some groups of mice were tested repeatedly, while other groups were subjected only to a single exposure. The observed locomotor activity, measured as horizontal activity and total distance travelled, indicated that the development of tolerance and of withdrawal symptoms to alprazolam is not related to repeated exposure of the mice to the experimental set-up, but is due to changes in function of the GABAa receptor.
Influence of FK506, Cyclosporin A, Testosterone and Nimodipine on	Motoneuron Survival Following Axotomy
Authors: Tao R. , Aldskogius H.
Published: December 2024

Injury to immature motoneurons results in extensive nerve cell death. Avulsion injury in adult animals has a similar effect. Rescuing injured neurons from degeneration and death is a prerequisite for succesful functional recovery. Here, we have explored the possible survival promoting effect of the immunosuppressant agents FK506 and cyclosporin A, the calcium channel blocker nimodipine as well testosterone on axotomized neonatal facial motoneurons. In addition, we examined the effect of cyclosporin A and Nimodipine, a calcium channel blocker, on survival of adult motoneurons following hypoglossal nerve avulsion. FK506 and cyclosporin A were administered intraperitoneally, testosterone intramuscularly and Nimodipine via the food. After the appropriate postoperative survival periods, the number of surviving facial or hypoglossal motoneurons respectively was calculated. FK506 and Cyclosporin A were found to enhance facial motoneuron survival following neonatal axotomy. Cyclosporin A and Nimodipine were found to promote motoneuron survival in adult rats after hypoglossal nerve avulsion. Nimodipine possibly also reduced motoneuron death in neonatal rats twenty-one days after facial nerve transsection, but failed to rescue motoneurons in neonatal rats during the first seven days after nerve injury. Treatment with testosterone was ineffective in preventing neonatal facial motoneurons from axotomy-induced death at seven days postaxotomy. The restults indicate that motoneuron degeneration can be counteracted to a large extent by immunosuppressant agents as well as by calcium channel blockers. Taken together with findings form previous studies, we conclude that motoneuron survival following axotomy can be promoted by a variety of endogenous and exogenous molecules acting on different cellular mechanisms.
Neural Cell Adhesion Molecule L1 Promotes Regeneration of Injured	Optic Nerve of Rats
Authors: Izumoto Shuichi , Ohnishi Takanori , Hirano Shun-ichiro , Hiraga Shoju , Arita Norio
Published: December 2024

Neural cell adhesion molecule L1 is a member of the immunoglobulin superfamily; it plays an important role in neurite outgrowth in vitro. We present evidence that the transected optic nerve in adult rats was promoted to regenerate by transplanted L1-expressing cells that were embedded in the Matrigel matrix. To obtain the maximum effects, a very careful operative procedure by which both stumps remained attached and the blood supply was preserved was essential. Visual evoked potential was partially recovered and traced fibers were seen to pass through the lesion site 7 weeks after optic nerve transection. Immunohistochemical analysis demonstrated that neurofilament-positive fibers were present around the site of experimental lesion. Our in vivo study demonstrated that L1 promoted the regeneration of the lesioned optic nerve in rats under strictly controlled environmental conditions.
Modeling Pediatric Head Trauma: Mechanisms of Degeneration	and Potential Strategies for Neuroprotection
Authors: Bittigau Petra , Pohl Daniela , Sifringer Marco , Shimizu Hiroki , Ikeda Masuhiro , Ishimaru Masahiko , Stadthaus Daniel , Fuhr Susanne , Dikranian Krikor , Olney John W. , Ikonomidou Chrysanthy
Published: December 2024

We have developed a model for head trauma in infant rats in an attempt to study mechanisms of neurodegeneration in the developing brain and were able to morphologically characterize two distinct types of brain damage. The first type or primary damage evolved within 4 hrs after trauma and occurred by an excitotoxic mechanism. The second type or secondary damage evolved within 6-24 hrs and occured by an apoptotic mechanism. Primary damage remained localized to the parietal cortex at the site of impact. Secondary damage affected distant sites such as the cingulate/retrosplenial cortex, subiculum, frontal cortex, thalamus, hippocampal dentate gyrus and striatum. Histological evidence of delayed cell death was preceded by decrease of bcl-2- in conjunction with increase of c-jun-mRNA-levels, already evident at 1 hr after trauma. Increase of CPP32-like activity and elevated concentrations of oligonucleosomes in affected brain regions represented additional findings to indicate that this secondary disseminated degenerative reaction is apoptotic in nature. At the age of 7 days, secondary apoptotic damage was more severe than primary excitotoxic damage, but its severity declined with increasing age. In 7-days-old rats, NMDA antagonists protected against primary excitotoxic damage but increased severity of secondary apoptotic damage whereas the free radical scavenger SPBN, the tumor necrosis factor (TNF) inhibitor pentoxifylline and the antioxidant N-acetylcystein mitigated apoptotic damage. These findings demonstrate that in the developing rat brain apoptosis and not excitotoxicity determines neuropathologic outcome following head trauma. Whereas radical scavengers and TNF-inhibitors may prove useful in treatment of pediatric head trauma, great caution should be applied in regards to the use of NMDA antagonists because of the inherent risk of apoptosis promotion.
Biochemical changes and gene expression following traumatic brain	injury: Role of spreading depression
Authors: Hermann Dirk Matthias , Mies Günter , Hossmann Konstantin-Alexander
Published: December 2024

The effects of spreading depression-like DC depolarizations on biochemical changes and gene expression were examined following trau-matic neocortical lesions, as induced by transcranial cold injury. The surrounding of traumatic cold lesions was characterized by increased glu-cose and lactate contents, without major disturbances of protein synthesis or energy state. A transient pH decrease by 0.4 units was noticed 1 h post-injury, which shifted towards alkaline values by 3 h. These changes were similar in animals with spontaneous spreading depression-like DC shifts (n = 14) and those without spreading depressions (n = 7), but there was a marked difference in the gene response. In injured animals without SD, only a short-lasting response of c-fos, junB, c-jun and MKP-1 mRNAs as well as c-Fos protein was bilaterally found in the piri-form cortex, and - with ipsilateral dominance - the dentate gyrus and hippocampal CA3/4 fields at 1 h after lesioning. In injure d animals with spreading depressions, on the contrary, a strong elevation was seen in layers II-IV and VI of the injury-remote ipsilateral cerebral cortex, which persisted over as long as 6 h. The expression of c-fos, junB and MKP-1 mRNAs was closely related to the time interval between the last spreading depression and the end of the experiments. Levels were highest shortly after transient DC shifts, and decreased thereafter mono-exponentially with half-lives of 48, 75 and 58 min for c-fos, junB and MKP-1 mRNAs, respectively. Thus, spreading depression is a prominent factor influencing the trauma-related gene response, but - in contrast to focal ischemia - it does not aggravate the metabolic dysfunction.
Assessment of sensorimotor functions after traumatic brain injury	(TBI) in childhood Methodological aspects
Authors: Jöhnk Kerstin , Kuhtz-Buschbeck Johann P. , Stolze Henning , Serocki Götz , Kalwa Sabine , Ritz Annegret , Benz Barbara , Illert Michael
Published: December 2024

Various basic qualitative and quantitative methods for the evaluation of sensorimotor functions after Traumatic Brain Injury (TBI) are introduced and discussed. Methodological aspects are illustrated by a single case follow-up study of a child after severe TBI (age 11; 712;1 yrs; 6, 8 and 12 month post TBI) in comparison to an age-matched healthy control group (N=16). The evaluation consisted of neurological investigation, Barthel-Index, Terver Numeric Score for Functional Assessment, Rappaport Disability Rating Scale (modified version), a coordination-test for children (KTK), a pilot-tested Motor Function Score, quantitative evaluation of spatiotemporal gait parameters on a walkway and on a treadmill, and the kinematic assessment of hand motor functions. Quantitative movement analyses revealed two general types of motor disorder: Slowing of movements and compensatory motor strategies. Averaged z-scores showed deficits, which were pronounced in fine motor skills (hand movements: 1.86, gait: 1.3). During follow-up, a strong improvement rate during the first (-0.48 z-scores) and nearly no improvement rate (-0.03 z-scores) during the second time interval was seen. Clinical scores and developmental tests were not able to document the whole restitutional course, whereas motor tests with special emphasis on functional aspects and the quantitative movement assessment seemed to be suitable methods. We conclude that a sufficient evaluation of sensorimotor functions after TBI in childhood needs an increase in procedural uniformity on onehand and the combination of various qualitative and quantitative methods on the other hand. To connect both claims, further research is necessary.
Differences in memory impairment and response to GM1 ganglioside	treatment following electrolytic or ibotenic acid lesions of the nucleus	basalis magnocellularis
Authors: Lescaudron Laurent , Stein Donald G.
Published: December 2024

Alzheimer's disease is a progressive dementia associated with cholinergic cell loss in the nucleus of Meynert that induces deficiencies in cholinergic neurotransmission in the neocortex. The nucleus basalis magnocellularis (NBM) is the rodent homologue to the nucleus of Meynert in humans. In this study, we examined the effects of GM1 ganglioside, a neuroprotective agent, on morphological and functional recovery after electrolytic or ibotenic acid lesions of the NBM. In animals, GM1 ganglioside has been shown to reduce some of the behavioral deficits that follow Central Nervous System lesions. Electrolytic or ibotenic acid lesions produced deficits in passive avoidance learning, as assessed by the number of trails taken to acquire the avoidance response. Only the electrolytic lesions impaired spatial memory in the Morris Water Maze (MWM), and GM1 administration did not improve performance on this task. Facilitation of passive avoidance acquisition was observed in animals receiving GM1 treatment after electrolytic or ibotenate lesions. Both types of injuries induced equivalent amounts of damage to the nucleus basalis but the electrolytic lesions produced greater damage to adjacent structures that could be responsible for the additional deficits observed on the MWM task.
Antimyoclonic and neuroprotective effects of lamotrigine in an	animal model of cardiac arrest
Authors: Kanthasamy Anumantha G. , Tith Tevy , Nguyen Bang , Tran Amy , Truong Daniel D.
Published: December 2024

A major consequence of severe cardiac arrest is impairment of neurological functions. Posthypoxic myoclonus and seizures are two of the major neurological problems following ischemic and hypoxic insults. This condition affects motor function to different degrees of severity ranging from mild to serious debilitation. The pathophysiological mechanism(s) associated with these neurological conditions remain elusive. Glutamate-mediated neuronal overexcitation is thought to play a major role in the neuronal damage and in the neurological consequences of the posthypoxic state. Therefore, lamotrigine, a new anticonvulsant that indirectly modulates glutamatergic neurotransmission by interfering with voltage-dependent sodium channels, was tested for its effectiveness in controlling the neurological and histopathological changes in the animal model of cardiac arrest-induced myoclonus. Lamotrigine dose-dependently attenuated the audiogenic seizures and action myoclonus seen in this rat model. Histological analysis using Nissl staining and the novel Fluoro-Jade histochemistry in cardiac-arrested rats showed an extensive neuronal degeneration in the hippocampus and cerebellum. Lamotrigine treatment significantly attenuated the neuronal degeneration in these brain areas. The neuroprotective effect was more pronounced in hippocampal pyramidal and cerebellar Purkinje neurons. The therapeutic window of lamotrigine in this model was 8 hours. These results suggest that lamotrigine can be viewed as a potential antimyoclonic and neuroprotective agent for the treatment of posthypoxic myoclonus and seizures. The study also suggests that neuronal hyperexcitability may play a role in the etiology of posthypoxic myoclonus and seizure.
Insulin-like growth factor-I promotes nerve regeneration through a	nerve graft in an experimental model of facial paralysis
Authors: Thanos Panayotis K. , Okajima Seiichiro , Tiangco David A. , Terzis Julia K.
Published: December 2024

Among the pathological sequelae of facial paralysis is a paralytic eye. Apart from the psychological and aesthetic deficits, facial paralysis if left untreated can lead to dryness, ulceration and eventual blindness. Although numerous restorative microsurgical approaches have been introduced to address the sequelae of this problem, complete restoration of function to denervated facial muscles remains elusive. Utilizing the rat model of facial paralysis the present research has as an objective to examine a dual treatment approach. Specifically, this study combined the current microsurgical treatment of the cross-facial nerve graft with local administration of insulin-like growth factor I (IGF-I). The efficacy of this combined approach (cross-facial nerve graft + IGF-I) was assessed in the following ways: (a) behavior measurement of the blink response and (b) histomorphometry light and electron microscopy of the entire nerve graft. These data will help provide insight into the restoration of facial muscle function after trauma and assist in the future development of more potent treatment strategies. 7he local adnünistration of IGF-I (50 µg/ml) to the cross-facial nerve graft was found to restore the blink response faster and to strengthen the degree of eye closure. Light microscopy examination revealed that IGF-I significantly enhanced axonal regeneration within a nerve graft (a 22% increase in the mean number of axons), and increased the mean nerve fiber diameter and myelin thickness. Electron microscopy assessment of the nerve grafts demonstrated that the IGF-I treated grafts possessed a greater density of microtubules, which were evenly distributed within the axoplasm.
Role of neurotrophins in neural plasticity: what we learn from the	visual cortex
Authors: Berardi N. , Lodovichi C. , Caleo M. , Pizzorusso T. , Maffei L.
Published: December 2024

A role for neurotrophins in regulating cortical developmental plasticity has clearly emerged in these last years. In this review we first present a summary of the early data on the action of NGF in visual cortical development and plasticity in the rat and of the actions of the other neurotrophins in the visual cortex of other mammals. In addition, in order to clarify the differerences in the results obtained with the various neurotrophins in different animal preparations we also report new data on the action of NGF, BDNF, NT3 and NT4 in the same preparation, namely the visual cortex of the rat. We discuss old and new results in a physiological model where different neurotrophins play different roles in regulating visual cortical development and plasticity by acting on different neural targets, such as LGN afferents, intracortical circuitry and subcortical afferents and propose a tentative scheme summarizing these actions.
Conditioning hypoxia causes protection against ischemia in the CA	1-region of hippocampal slices
Authors: Rüthrich Heide-Linde , Krug Manfred
Published: December 2024

Purpose: At present the mechanisms of ischemic or hypoxic tolerance are not fully understood at the cellular level. Methods: In order to further characterize the effects of conditioning hypoxia on the synaptic transmission in the hippocampal area CA1, rats were exposed to a moderate normobaric hypoxia for 8 h. Transverse hippocampal slices were prepared 1, 7 or 14 days after this conditioning hypoxia and evoked field potentials were recorded in the CA 1 region upon stimulation of the Schaffer collaterals before, during and up to 4 h after ischemia in vitro (hypoxia and reduced glucose). Results and Conclusions: The time to disappearance of the evoked potential during ischemia was significantly prolonged after seven, but not after one or 14 days in slices taken from conditioned animals. In addition the input/output (I/O) curves of evoked potentials were not altered 4 h after the ischemia. In contrast, the time to disappearance of the evoked potentials was shorter and the I/O curves were diminished in slices from control animals. Possible mechanisms of the protective effect are discussed.
System-wide repercussions and adaptive plasticity: the sequelae of	immature visual cortex damage
Authors: Payne Bertram R.
Published: December 2024

Damage of primary visual cortex in mature mammals severely disrupts vision by disconnecting much of the cognitive processing machinery of extrastriate cortex from its source of visual signals in the retina. However, equivalent lesions incurred early in postnatal life unmask a substantial latent flexibility of the brain to minimize the disruption by specific and ordered pathway expansions that bypass the lesion. The expansions shape pathways from retina through thalamus to extrastriate cortex and onto the midbrain into new, useful forms that are retained into adult life. These useful modifications support relatively normal signal processing in a variety of structures and the sparing of certain visually guided behaviors, such as aspects of complex-pattern vision and localizing objects introduced into the visual field. Thus, both the brain and the individual are optimized, in the absence of primary visual cortex, by adaptations for useful interactions with the environment. So far, the repercussions of early visual cortex lesions have been most thoroughly documented in cats, although it is likely on the basis of known repercussions and similarity of visual system organization and developmental sequence, that broadly equivalent repercussions and adaptations occur in monkeys and humans following early lesions of primaiy visual cortex. The knowledge gained has implications for devising therapeutic strategies to attenuate defects in vision induced by cortical lesions.
Local application of extracellular matrix proteins fails to reduce	the number of axonal branches after varying reconstructive surgery on rat	facial nerve
Authors: Dohm Stephan , Streppel Michael , Guntinas-Lichius Orlando , Pesheva Penka , Probstmeier Rainer , Walther Michael , Neiss Wolfram F. , Stennert Eberhard , Angelov Doychin N.
Published: December 2024

Purpose: A major reason for the poor functional recovery after peripheral nerve injury is the outgrowth of supernumerary axonal branches at the lesion site. Projecting within several nerve fascicles, the branches of one axon often re-innervate synchronously muscles with antagonis-tic functions and impair any coordinated activity. We hypothetized that accelerated axonal elongation through extracellular matrix proteins fos-tering neurite outgrowth might reduce axonal branching and improve recovery of function. Methods: In a control group of rats, ramus zygomaticus, ramus buccalis, and ramus marginalis mandibulae of the facial nerve were transected and the stumps labeled with DiI, Fluoro-Gold (FG), and Fast Blue (FB). Results: Neuron counts showed that the zygomatic ramus contained axons of 204 ± 88 DiI-labeled motoneurons in the dorsal facial subnu-cleus. No perikarya were labeled by 2 or 3 tracers. After transection and suture of the facial nerve trunk, the zygomatic ramus contained axons of 328 ± 50 motoneurons dispersed throughout the whole facial nucleus. The occurrence of double-labeled (DiI+FG and DiI+FB) motoneu-rons showed that about 30 % of all axons in the zygomatic ramus had a twin branch projecting within the buccal and/or mandibular ramus. Conclusions: Entubulation of transected facial nerve in a silicone tube containing phosphate buffered saline, collagen type I, laminin, fibronectin, or tenascin did not reduce the portion of double-labeled motoneurons. We conclude that (i) axonal branching follows a rather con-stant pattern regardless of changes in the local microenvironment; (ii) despite their known effect to support neurite outgrowth, all tested extra-cellular matrix proteins do not suppress axonal branching in the rat facial nerve model.
Long-term TGFâ2 protein expression in heterotopic cortical	grafts located in the rat striatum
Authors: Sabel Michael , Kiessling Marika , Sommer Clemens
Published: December 2024

Purpose: Transforming growth factor beta 2 (TGFâ2) is a multifunctional cytokine thought to play a crucial role in neuronal growth, differ-entiation and survival. In the cortex of adult rats, TGFâ2 is constitutively expressed in a subset of neurons and astrocytes. In the present study we analyzed whether TGFâ2 is also present in intrastriatal transplants of cortical anlage. In addition we investigated the temporo-spatial expression pattern of TGF2 in âthe surrounding host striatum. Methods: Cortical primordia of rat fetuses (E14) were stereotactically grafted into the rostral striatum of adult recipient rats. Grafts were allowed to differentiate for 1, 2, 3, 4, 8 weeks or one year, respectively, followed by morphological and immunohistochemical analysis. Results: From week 2 on, TGFâ 2-immunoreactivity (IR) was detectable in transplanted neurons. Within the graft, GFAP-IR was already present one week after transplantation, whereas TGFâ2-immunostained astrocytes were first seen after 2 weeks. One year after transplanta-tion, TGFâ2 positive neurons and astrocytes were still present. In the host striatum and at the graft-host interface an increase of TGFâ2-immu-noreactive astrocytes first occured after one week both in grafted animals and in sham-operated (lesioning without grafting) rats. Conclusions: Our data suggest that at least a subpopulation of transplanted neurons develops a phenotype as cortical neurons in situ with respect to TGFâ2 expression. Upregulation of astrocytic TGFâ2 expression within the graft, however, is due to the trauma imposed by the transplantation procedure rather than an intrinsic differentiation program of co-grafted astrocytes.
Target-dependent axonal sprouting following vagal-hypoglossal	nerve anastomosis in cats
Authors: Lan Chyn Tair , Liu Jiang Chuan , Ling Eng Ang , Cheng Min Hsiung , Youn Su Chung
Published: December 2024

Purpose: To investigate the relationships between the axonal sprouting and target neurotization by central neurons after nerve heterocon-nection. Methods: Unilateral (right) vagal-hypoglossal nerve anastomosis (VHA) was performed in adult cats. Following 3315 days postoperation (dpo), quantitative analyses and ultrastructural changes in the proximal portion of the vagal-hypoglossal heteroconnected nerve as well as the time course of neuronal regeneration were studied. Along with this, horseradish peroxidase (HRP) retrograde tracing technique was used to label the neurons of dorsal motor vagal nucleus (DMV) and nucleus ambiguus (NA) to ascertain if target neurotization was established. Results: The contralateral (left) intact vagus nerve proximal to the level of ansa cervicalis showed an average of 33 ± 1 myelinated and 74 ± 4 unmyelinated axons in 727 µm 2 sectional area of the nerve. In the heteroconnected nerve at the corresponding level just proximal to the anastomosis site, there was a marked increase in the number of small axons sprouting from the unmyelinated nerve fibers between 18 and 25 dpo. The number of these axonal sprouts appeared to decline at 32 dpo but its increase of 131 % was sustained until the late regeneration stage at 315 dpo when compared with the contralateral nerve serving as a control. The mean number of myelinated axons per area unit (727 µm 2 ) was reduced to 18 at 3 dpo but was immediately restored to the normal range at 7 dpo. The retrograde labelling of neurons in both the DMV and NA was first detected at 22 dpo and was progressively increased peaking by about 67 dpo. Conclusions: We conclude that compared with the unmyelinated axons, the myelinated axons may acquire a superior interaction with the new target. Furthermore, the postoperative neurotization of tongue muscles may initiate and facilitate the retraction of the redundant axonal sprouts.
Proteins in cerebrospinal fluid and blood: Barriers, CSF flow rate	and source-related dynamics
Authors: Reiber Hansotto
Published: December 2024

Cerebrospinal fluid (CSF) routine analysis for diagnosis of neurological diseases is based on the concepts for discrimination of blood-derived and brain-derived immunoglobulin fractions in CSF. The actual molecular flux/CSF flow theory of the blood/CSF barrier function, which founded the hyperbolic discrimination lines in quotient diagrams, is derived from the laws of molecular diffusion combined with CSF flow rate. It emerged from this theory that the decrease of CSF flow rate is sufficient to explain quantitatively the increase of CSF protein concentrations as observed in many neurological diseases. With this concept of CSF flow rate as the modulator of the normal and pathological blood-CSF barrier function, we got for the first time a theoretical frame work to explain also quantitatively the dynamics of brain-derived proteins and their source related (neurons and glial cells or leptomeningal cells) differences. The review of the anatomical, physiological and biophysical knowledge points to the new interpretations: The changing albumin quotient is an indicator of changing CSF flow rate and not for a morphological "leakage" of the blood-brain barrier.

As an application of these concepts the dynamics of brain-derived molecules in blood are discussed with two examples: beta trace protein, flowing with CSF into venous blood, and neuron-specific enolase, passing from tissue into blood the opposite direction of serum proteins, again a gradient-dependent protein diffusion across the intact blood vessel wall.
The Janus face of glial-derived S100B: Beneficial and detrimental	functions in the brain
Authors: Van Eldik Linda J. , Wainwright Mark S.
Published: December 2024

Glia play active and vital roles in the CNS, including regulation of brain development, maintenance of cellular homeostasis and reparative responses to acute and chronic neurologic insults. However, in pathological conditions, glial function may be dysregulated resulting in enhanced neuroinflammation and further neurologic injury. The fundamental concept that aberrant regulation of a normally beneficial process may instead result in pathology is exemplified by the properties of the glial-derived protein, S100B. In the developing brain and following acute glial activation in response to injury, S100B acts as a neurotrophic factor and neuronal survival protein. In contrast, overproduction of S100B by activated glia can lead to exacerbation of neuroinflammation and neuronal dysfunction. This duality of S100B actions, both reparative and degenerative, is consistent with the compelling clinical evidence of the association between increases in S100B levels and outcome following brain injury. S100B levels generally correlate with the severity of damage and may have predictive value for adverse neurological outcomes. The cumulative data support the potential of S100B as a biomarker for brain damage, implicate glial activation as a possible treatment target in acute and chronic CNS disorders, and highlight the dual role of glia in the reparative and pathologic responses to neurologic injury.
Molecular markers of brain damage – clinical and ethical	implications with particular focus on cardiac arrest
Authors: Snyder-Ramos Stephanie A. , Böttiger Bernd W.
Published: December 2024

Although 25–50% of patients suffering from cardiac arrest can be stabilised haemodynamically, the hospital discharge rate is only 2–14%. One of the major causes of this discrepancy is persistent brain damage. Studies to assess the prognostic value of early prediction of neurologic and overall outcome in patients with cardiac arrest have not yet produced precise and generally accepted diagnostic rules. As apparative diagnostic methods often fail to predict neurologic outcome, the role of molecular markers has come a focus of common interest for early outcome prediction.

This systematic review article aims to give an overview on the most important molecular markers for neurologic and overall outcome prediction and outline the advantages, clinical implications and ethical issues in patients undergoing cardiopulmonary resuscitation after cardiac arrest.

For this purpose, the traditional marker for brain damage, the neuron-specific enolase, a gamma gamma isomer of enolase and cytoplasmatic enzyme of glycolysis, and the astroglial protein S100, a calcium-binding protein regulating neuronal differentiation, outgrowth, and apoptosis, are analysed and their role discussed as a marker for brain damage in general and recovery after cardiopulmonary resuscitation following cardiac arrest. Neuron-specific enolase has been investigated as a neuro-marker after brain damage and for outcome prediction in unconscious patients. Whereas the protein S100 has proven to be a good marker for neuronal damage after isolated brain injury, its role in cardiac surgery is not as clear: at least, in the early postoperative phase S100 is not a sole marker for neurologic damage, as release of S100 from cardiac tissue and other sources has also been demonstrated. However, the persistent elevation of S100 after cardiac surgery is specific for neurologic impairment.

Most interestingly, after cardiac arrest the protein S100 has shown to be a good survival marker for overall outcome prediction. Although it cannot be absolutely determined whether cerebral or cardiac release of S100 is predominant in this clinical setting, recent studies have revealed that S100 serum levels are a useful diagnostic tool for outcome prediction. In contrast, after cardiac arrest serum levels of protein S100 did not reach a 100% specificity and sensitivity in clinical studies, and, therefore, elevated S100 in these patients has to be interpreted with caution. Nonetheless, low S100 serum levels have been correlated with good outcome and, therefore, even if all other diagnostic tests indicate poor outcome, all therapeutic efforts must be undertaken, as no single study has shown that normal S100 serum levels were associated with poor prognosis.
Biochemical serum markers for brain damage: A short review with	emphasis on clinical utility in mild head injury
Authors: Ingebrigtsen Tor , Romner Bertil
Published: December 2024

Purpose. To provide an overview of clinical research on the use of biochemical serum markers for traumatic brain injury (TBI) in the evaluation of patients with mild head injuries (MHI).

Methods. The MEDLINE database was searched for publications on biochemical serum markers of TBI until August 2002. Clinical studies addressing their use in MHI were reviewed.

Results. Desirable characteristics for biochemical serum markers of TBI were identified. Creatine kinase isoenzyme BB (CK-BB), neuron specific enolase (NSE) and S-100B protein have been most extensively studied. The sensitivity and specificity of CK-BB is inadequate for use as an indicator of traumatic brain injury. Serum levels of NSE do not correspond to the amount of TBI, probably because of its long (20 h) half-life. S-100B serum levels are correlated to both clinical measures of injury severity, neuroradiological findings and outcomes in several studies from different authors.

Conclusion. Currently, S-100B protein is the most promising marker for evaluation of TBI in patients with MHI.
Impairment-oriented Training (IOT) – scientific concept and	evidence-based treatment strategies
Authors: Platz T.
Published: December 2024

Everyday activities can be affected by many different body dysfunctions (impairments). A multi-modal analysis of electric brain activity revealed that movement-related brain activity is differentially altered in patients with different impairments, i.e. paresis, somatosensory deficits, and apraxia. Each body dysfunction has its own characteristics in terms of the resulting sensorimotor control deficits. The Impairment-oriented Training concept intends to characterise the resulting sensorimotor control deficits for each impairment. Based on such analyses two specific training techniques have been developed for stroke patients with mild and severe arm paresis: (1.) The Arm Ability training for mild arm paresis trains different sensorimotor abilities such as dexterity, speed of isolated hand and finger movements, steadiness, aiming, or tracking under visual guidance. Improvement of these motor abilities leads to improved motor performance in every day life circumstances. (2.) The Arm BASI S training for severe arm paresis intends to restore more basic motor control, i.e. the full range of active non-segmented motion of all limb segments, both postural activities and dynamic motion control, interjoint-coordination, and adequate motor control when external forces are applied. Clinical trials with representative study populations supported both techniques' clinical efficacy.
Peripheral nerve regeneration through a synthetic hydrogel nerve	tube
Authors: Belkas Jason S. , Munro Catherine A. , Shoichet Molly S. , Midha Rajiv
Published: December 2024

Purpose: As alternatives to nerve grafts for peripheral nerve repair, we have synthesized 12 mm long poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous tubes and studied their regenerative capacity for the repair of surgically-created 10 mm rat sciatic nerve gaps. We compared the in vivo regenerative efficacy of these artificial tubes with the gold standard, the nerve autograft.

Methods: Tubes were assessed in vivo for their ability to support nerve regeneration at 4, 8, and 16 weeks post-implantation by histology, electrophysiology, histomorphometry, and reinnervated lateral gastrocnemius (LG) dry muscle mass.

Results: Axonal regeneration within the tubes was observed by 8 weeks, with outcome parameters comparable to autografts. This finding was further supported by the electrophysiological and histomorphometric results. The 16 week tube group had a bimodal response, with 60% of the tubes having a similar response to autografts and the other 40% having significantly lower (p < 0.05) outcome measures in several parameters.

Conclusions: Axonal regeneration in artificial tubes was similar to that in autografts at 8 and 16 weeks, however, a bimodal distribution of regeneration was observed in 16 week tubes.
Administration of monoclonal antibodies neutralizing the	inflammatory mediators tumor necrosis factor alpha and interleukin -6 does not	attenuate acute behavioral deficits following experimental traumatic brain	injury in the rat
Authors: Marklund Niklas , Keck Carrie , Hoover Rachel , Soltesz Kristie , Millard Marie , LeBold David , Spangler Zachary , Banning Adrian , Benson Jacqueline , McIntosh Tracy K.
Published: December 2024

Purpose: Although many previous studies have indicated that the acute inflammatory response following traumatic brain injury (TBI) is detrimental, inflammation may also positively influence outcome in the more chronic post-injury recovery period. We evaluated the effects of monoclonal antibodies (mAB), neutralizing either IL-6 (IL-6 mAB) or TNF-α (TNF mAB), administered intracerebroventricularly (i.c.v) on acute neurobehavioral outcome following TBI.

Methods: Male Sprague-Dawley rats (n = 173) were anesthetized (sodium pentobarbital, 60 mg/kg) and subjected to lateral fluid percussion (FP) brain injury of moderate severity (n = 123) or sham injury (n = 50). Beginning 1 h post-injury, TNF mAB (n = 41, of which 25 were brain-injured) or IL-6 mAB (n = 42, of which 25 were brain-injured) at a concentration of 2 mg/mL was infused i.c.v ipsilateral to the injury for 48 hours. Vehicle-treated animals (control IgG; n = 43, of which 26 were brain-injured) served as controls. In Study 1, cognitive function was evaluated in the Morris Water Maze (MWM) followed by evaluation of regional cerebral edema at 48 h post-injury. In Study 2, animals were evaluated for neurological motor function and post-injury learning in the MWM at one week post-injury.

Results: FP brain injury caused significant cognitive (p < 0.05) and neurological motor (p < 0.05) deficits and increased regional brain water content in the injured hemisphere. Treatment with either TNF- or IL-6-mAB had no effect on neurological motor, cognitive function or brain edema during the first post-injury week.

Conclusions: Evaluation of anti-inflammatory mABs on more chronic behavioral deficits appears warranted.
Unilateral pallidotomy produces motor deficits and excesses in	rats
Authors: Byler S.L. , Shaffer M.C. , Barth T.M.
Published: December 2024

Purpose: To better understand the behavioral effects of pallidotomy as a treatment for a range of movement disorders, including Parkinson's disease, chorea, and ballismus. In some cases, pallidotomy increases movement whereas in others it decreases unwanted motor behavior. Method: The present study investigated the effects of unilateral pallidotomy in rats with an otherwise healthy nervous system. Pallidotomized and sham lesion rats were evaluated on a battery of tests that measure sensorimotor behavior. Results: Compared to sham lesion controls, pallidotomized rats showed motor deficits (forelimb placing; bracing) and excesses (locomotor behavior) as well as sensorimotor asymmetries (ipsilateral adhesive patch bias; increased contralateral foot faults). Conclusion: Motor deficits observed after pallidotomy were similar to those reported in previous research from this and other laboratories following damage to the nigrostriatal pathway or sensorimotor cortex. Motor excesses after pallidotomy are consistent with current theories of globus pallidus function. Taken together, these data suggest hypokinetic effects of pallidotomy may be related to fibers of passage (i.e. internal capsule), while hyperkinetic effects may be related to damage of pallidal cell bodies. These data may have important clinical implications because they suggest that regardless of the state of existing pathology, pallidotomy may create unwanted behavioral side effects.
Temporal factors in peripheral nerve reconstruction with suture	scaffolds: An experimental study in rodents
Authors: Keune Jason D. , Brenner Michael J. , Schwetye Katherine E. , Yu Jeffery W. , Fox Ida K. , Hunter Daniel A. , Mackinnon Susan E.
Published: December 2024

Purpose: This study investigated nerve regeneration following nerve repair with longitudinally oriented sutures, with emphasis on timing. Prior work in rodents has shown that suture scaffolds are comparable to nerve grafting when assessments are made at late time points. However, rodents have exceptional regenerative capacity, making it difficult to detect key differences at late time points. This study therefore investigated regeneration across suture scaffolds both at early (4 week) and late (12 week) endpoints.

Methods: Rodents were randomized to nerve gap, transection and repair, nerve grafting, and suture scaffold groups. Nerve regeneration was evaluated at 4 and 12 weeks. Histomorphometry parameters were evaluated using binary image analysis of toluidine blue-stained nerve cross sections.

Results: Compared to nerve grafts, suture scaffolds were associated with significantly decreased neural density (4208 ± 3546 vs. 193 ± 416, fibers/mm $^2$ , p<0.05) and fiber width (1.92 ± 1.21 vs. 0.75± 1.16, μm, p<0.05). At 12 weeks, differences between groups were no longer detectable.

Conclusion: When evaluated at optimal time points for rodents, suture scaffolds fail to support regeneration comparable to the existing gold standard of nerve grafting. This finding raises significant concerns regarding the clinical application of suture scaffolds.
rTMS combined with motor learning training in healthy	subjects
Authors: Carey James R. , Fregni Felipe , Pascual-Leone Alvaro
Published: December 2024

Purpose. This study explored the effects of motor learning training combined with repetitive transcranial magnetic stimulation (rTMS) on motor performance in healthy subjects.

Methods. Twenty-seven right-handed subjects were randomized to three groups: ipsilateral rTMS (IS group), contralateral rTMS (CS group), and sham rTMS (SS group). rTMS was applied for 10 minutes (1 Hz, 90% motor threshold) prior to training. Training involved 10 minutes of finger tracking with the right hand. Tracking performance was tested before, during and after training.

Results. Improvement in tracking performance over the posttests was not significantly different between the CS and SS groups, whereas it was significantly lower for the IS group compared to the SS group. No difference was found across groups at retention tests.

Conclusion. These findings indicate that rTMS interfered with motor performance transiently when applied ipsilateral to the training hand and had no effect when applied contralaterally. These results invite further work to determine whether the disruptive effect of ipsilateral rTMS observed here in healthy subjects, with presumably balanced interhemispheric inhibition, might translate differently to subjects with abnormal interhemispheric inhibition (stroke patients) in a way that disinhibits the ipsilesional hemisphere and improves performance in the paretic hand.
Corticosteroid decreases subventricular zone cell proliferation,	which could be reversed by paroxetine
Authors: Lau Wui-Man , Qiu Guang , Helmeste Daiga M. , Lee Tatia M.C. , Tang Siu-Wa , So Kwok-Fai , Tang Siu-Wa
Published: December 2024

Purpose: Major depressive disorder is often associated with elevated glucocorticoid levels, which in turn suppress cell proliferation and neurogenesis in the hippocampus. Increasing evidence supports that antidepressants induce hippocampal neurogenesis and this induces speculation that decrease in hippocampal neurogenesis has causal relationship with depression. There is, however, a lack of information about neurogenic effects of antidepressants on the subventricular zone, which is another CNS region with continuous neurogenesis throughout adulthood. In the present study, we investigated whether corticosterone and the SSRI paroxetine, have effects on SVZ cell proliferation.

Methods: Rats were treated with the corresponding drugs for 14 days and the proliferating cells were labeled with bromodeoxyuridine (BrdU). BrdU labeled cells in the SVZ were quantified and analyzed.

Results: In the corticosterone-treatment group, cell proliferation was decreased by 18% compared to vehicle-treatment group. Paroxetine-treatment group, in contrast, shows a 34% increase in cell proliferation. The decreased cell proliferation caused by corticosterone was prevented by paroxetine.

Conclusions: Although corticosterone and antidepressants were found to affect cell proliferation in hippocampus, this is the first report to demonstrate that 1) corticosterone decreases cell proliferation in SVZ; 2) paroxetine promotes SVZ cell proliferation and 3) the suppressive effect on SVZ cell proliferation by corticosterone could be attenuated by paroxetine. These findings provide new insights into basic mechanisms of antidepressants, potential impact of steroid therapy on CNS neurogenesis, antidepressant mechanisms of action and potential involvement of the olfactory system in depression.