bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of synaptic inhibition during cerebral ischemia in rats and rabbits.
Authors: Lyden P D , Hedges B 
Published: June 2011

Excitatory neurotransmitters appear to cause cell death during ischemia by inducing depolarization, influx of ions, and metabolic failure in the postsynaptic neuron. If this hypothesis is correct, then postsynaptic membrane hyperpolarization and inhibition of metabolism may be protective. Antagonists of the excitotoxic amino acid glutamate protect neurons in culture and in animal models of stroke but appear to cause unacceptable side effects in humans. We propose an alternative strategy of protection using agonists of the inhibitory neurotransmitter gamma-aminobutyric acid.
We caused multifocal cerebral ischemia in rats and rabbits by injecting microspheres into the carotid circulation. We administered saline, muscimol, or MK-801 within 5 minutes of stroke onset. We used a bioassay to measure outcome. In rats, we also used learning to assess cortical function, and we performed detailed quantitative brain morphometry 3 months after infarction.
Using the bioassay, we found that muscimol exerted a protective effect in rats (p less than 0.01). There was a dose-response effect seen in muscimol-treated rabbits. Rats treated with muscimol or MK-801 exhibited significantly better visual-spatial learning compared with saline-treated subjects (p less than 0.001). Hemisphere volume after ischemia was comparable in all groups.
Agonists of gamma-aminobutyric acid and antagonists of glutamate appear to protect brain during ischemia. Since agonists of gamma-aminobutyric acid are known to have fewer side effects in humans, they may prove more useful in the clinical setting as neuroprotective agents.
Tirilazad mesylate does not improve early cerebral metabolic recovery following compression ischemia in dogs.
Authors: Helfaer M A , Kirsch J R , Hurn P D , Blizzard K K , Koehler R C , Traystman R J 
Published: June 2011

Tirilazad mesylate (U74006F) has been reported to improve recovery following cerebral ischemia. We conducted a randomized blinded study to determine if the drug would improve immediate metabolic recovery after complete cerebral compression ischemia.
Mongrel dogs were anesthetized with pentobarbital and fentanyl and treated with either vehicle (citrate buffer, n = 8) or tirilazad (1.5 mg/kg i.v. plus 0.18 mg/kg/hr, n = 8). Normothermic complete cerebral compression ischemia was produced for 12 minutes by lateral ventricular fluid infusion to raise intracranial pressure above systolic arterial pressure. Cerebral high-energy phosphate concentrations and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Cerebral blood flow was measured with radiolabeled microspheres, and oxygen consumption was calculated from sagittal sinus blood samples. Somatosensory evoked potentials were measured throughout the experiment.
During ischemia, both groups demonstrated complete loss of high-energy phosphates and a fall in intracellular pH (vehicle, 5.76 +/- 0.23; tirilazad, 5.79 +/- 0.26; mean +/- SEM). At 180 minutes of reperfusion, there were no differences between groups in recovery of intracellular pH (vehicle, 6.89 +/- 0.07; tirilazad, 6.88 +/- 0.18), phosphocreatine concentration (vehicle, 89 +/- 16%; tirilazad, 94 +/- 24% of baseline value), oxygen consumption (vehicle, 2.6 +/- 0.2 ml/min/100 g; tirilazad, 1.8 +/- 0.5 ml/min/100 g), or somatosensory evoked potential amplitude (vehicle, 11 +/- 6%; tirilazad, 7 +/- 4% of baseline value). Forebrain blood flow fell below baseline levels at 180 minutes of reperfusion in the tirilazad-treated animals but not in the vehicle-treated dogs (vehicle, 28 +/- 4 ml/min/100 g; tirilazad, 18 +/- 5 ml/min/100 g).
We conclude that tirilazad pretreatment does not improve immediate metabolic recovery 3 hours following 12 minutes of normothermic complete ischemia produced by cerebral compression.
Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats.
Authors: Globus M Y , Wester P , Busto R , Dietrich W D 
Published: June 2011

Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed.
Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n = 5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 mg/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted.
Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean +/- SEM baseline, 1.86 +/- 0.25 pmol/ml perfusate; during ischemia, 8.14 +/- 0.89 pmol/ml; p < 0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98 +/- 0.15 pmol/ml; ischemia, 24.4 +/- 5.93 pmol/ml; p < 0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34 +/- 16 normal-appearing neurons, middle, 52.2 +/- 22.9 neurons; lateral, 56.6 +/- 21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6 +/- 6.5 neurons; middle, 131.4 +/- 4.9 neurons; lateral, 130 +/- 7.5 neurons; p < 0.01 different from nontreated).
Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage.
Diffusion-weighted imaging studies of cerebral ischemia in gerbils. Potential relevance to energy failure.
Authors: Busza A L , Allen K L , King M D , van Bruggen N , Williams S R , Gadian D G 
Published: June 2011

Diffusion-weighted magnetic resonance imaging has been shown to be particularly suited to the study of the acute phase of cerebral ischemia in animal models. The studies reported in this paper were undertaken to determine whether this technique is sensitive to the known ischemic thresholds for cerebral tissue energy failure and disturbance of membrane ion gradients.
Diffusion-weighted images of the gerbil brain were acquired under two sets of experimental conditions: as a function of cerebral blood flow after controlled graded occlusion of the common carotid arteries (partial ischemia), as a function of time following complete bilateral carotid artery occlusion (severe global ischemia), and on deocclusion after 60 minutes of ischemia.
During partial cerebral ischemia, the diffusion-weighted images remained unchanged until the cerebral blood flow was reduced to 15-20 ml.100 g-1.min-1 and below, when image intensity increased as the cerebral blood flow was lowered further. This is similar to the critical flow threshold for maintenance of tissue high-energy metabolites and ion homeostasis. After the onset of severe global cerebral ischemia, diffusion-weighted image intensity increased gradually after a delay of approximately 2.5 minutes, consistent with complete loss of tissue adenosine triphosphate and with the time course of increase in extracellular potassium. This hyperintensity decreased on deocclusion following 60 minutes of ischemia.
The data suggest that diffusion-weighted imaging is sensitive to the disruption of tissue energy metabolism or a consequence of this disruption. This raises the possibility of imaging energy failure noninvasively. In humans, this could have potential in visualizing brain regions where energy metabolism is impaired, particularly during the acute phase following stroke.
Neuroprotective effects of carvedilol, a new antihypertensive agent, in cultured rat cerebellar neurons and in gerbil global brain ischemia.
Authors: Lysko P G , Lysko K A , Yue T L , Webb C L , Gu J L , Feuerstein G 
Published: June 2011

Free radical generation mediates part of the ischemic neuronal damage caused by the excitatory amino acid glutamate. Carvedilol, a novel multiple-action antihypertensive agent, has been shown to scavenge free radicals and inhibit lipid peroxidation in swine heart and rat brain homogenates. Therefore, we studied the neuroprotective effect of carvedilol on cultured cerebellar neurons and on CA1 hippocampal neurons of gerbils exposed to brain ischemia.
Neuroprotective mechanisms were studied using an in vitro ischemia model of cultured rat cerebellar granule cell neurons exposed to either glutamate or oxygen free radical-generating systems. Prevention of lipid peroxidation by carvedilol was studied by measuring the formation of thiobarbituric acid-reactive substance. Gerbil CA1 neuron survival was examined by direct neuronal count 7 days after 6 minutes of global ischemia with reperfusion.
Carvedilol protected cultured neurons in a dose-dependent manner against glutamate-mediated excitotoxicity (inhibitory concentration [IC50] = 1.1 microM) as well as against a 20-minute oxidative challenge (IC50 = 5 microM). The IC50 against the oxidative challenge was lowered to 1.3 microM by growing neurons for 24 hours in the presence of carvedilol. At 10 microM carvedilol inhibited lipid peroxidation 50% and 73% (n = 4, p < 0.001) in neurons exposed to two different free radical-generating systems. Neuroprotection of 52% (n = 22, p = 0.009 versus vehicle) of gerbil CA1 hippocampal neurons was achieved by pretreatment and posttreatment with subcutaneous injection of 3 mg/kg carvedilol twice a day for 4 and 3 days, respectively.
Carvedilol provided neuroprotection in both in vitro and in vivo models of neuroinjury, where oxygen radicals are likely to play an important role. Therefore, carvedilol may reduce the risk of cerebral ischemia and stroke by virtue of both its antihypertensive action and its antioxidative properties.
Is cerebral angiography indicated in infective endocarditis?
Authors: van der Meulen J H , Weststrate W , van Gijn J , Habbema J D 
Published: June 2011

Patients with infective endocarditis may develop intracranial mycotic aneurysms. Whether these patients should undergo cerebral angiography followed by prophylactic surgery if an aneurysm is detected is an unresolved question.
We estimated the probability of survival 12 weeks after the diagnosis of infective endocarditis on the basis of data available in the literature.
For a 40-year-old female patient with right-sided hemiplegia, the 12-week survival is estimated to be 83.75% without angiography and 83.65% with angiography; the specific mortality of intracranial mycotic aneurysms is relatively small but increases by 40% (from 0.25% to 0.35%) if angiography is performed. The risk of aneurysm rupture in infective endocarditis and the mortality from rupture appear to be the most important factors that affect the analysis.
Cerebral angiography should not be performed routinely in patients with infective endocarditis. Specific subgroups in whom such a policy might be beneficial have not yet been identified.
99mTc-HMPAO-SPECT with acetazolamide challenge to detect hemodynamic compromise in occlusive cerebrovascular disease.
Authors: Knop J , Thie A , Fuchs C , Siepmann G , Zeumer H 
Published: June 2011

Insufficiency of collateral supply may lead to low-flow infarcts in severe occlusive cerebrovascular disease. The aim of this study was to evaluate the feasibility of technetium-99m-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) to assess hemodynamic compromise in the anterior circulation.
Cerebral blood flow before and after 1 g acetazolamide was analyzed by 99mTc-HMPAO-SPECT in 21 symptomatic patients with documented extracranial obstructions. SPECT findings were correlated with the results of angiography, transcranial Doppler sonography, and computed tomographic scan.
The acetazolamide-induced increase of cerebral blood flow could be reliably monitored by increase of cerebral 99mTc-HMPAO uptake, which varied between 11.4% and 47.6% in the less-affected hemisphere. Increment of hemispheric side-to-side asymmetry of tracer uptake after drug challenge revealed significant restriction of regional vasoreactivity in 11 patients. Agreement in assessing hemodynamic compromise was reached in 81% of patients with ophthalmic artery collaterals on angiography (p < 0.001), in 76% with low-flow infarcts on computed tomographic scan (p < 0.01), and in 91% with markedly reduced flow velocities on transcranial Doppler (p < 0.0001). One patient developed a low-flow infarct in the area predicted by SPECT during follow up.
We conclude that 99mTc-HMPAO-SPECT with acetazolamide challenge is a useful method for assessment of the adequacy of hemispheric collateral pathways in patients with severe occlusive cerebrovascular disease.
Features on initial computed tomography scan of infarcts with a cardiac source of embolism in the NINDS Stroke Data Bank.
Authors: Kittner S J , Sharkness C M , Sloan M A , Price T R , Dambrosia J M , Tuhrim S , Wolf P A , Mohr J P , Hier D B 
Published: June 2011

The lack of valid criteria for the clinical diagnosis of cardiogenic embolism is a major problem in both patient care and research. The aim of this study was to identify features on the initial computed tomogram of the brain that discriminate between patient groups with and without a cardiac source of embolism. To gain insight into the neuroradiological features relevant to the diagnosis of cardiac embolic stroke, we studied the initial computed tomogram of the 1,267 patients with ischemic stroke and such a scan in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank.
We analyzed the initial computed tomographic data from 1,267 patients with ischemic stroke in the NINDS Stroke Data Bank. Based solely on the presence of cardiac sources of embolism, we defined groups with high (n = 244), medium (n = 165), and low (n = 858) risk for cardiogenic embolism and compared the features on the initial computed tomogram among these three groups.
Patients in the high-risk group were significantly more likely (p < 0.001) to have infarcts involving one half lobe or larger or infarcts involving both superficial and deep structures than patients in the medium- or low-risk groups. In contrast, deep small infarcts had a negative association (p = 0.004) with the presence of a cardiac source of embolism. There was no significant trend across risk groups in the percent with hemorrhagic infarction, regardless of whether patients with anticoagulant use at the time of the stroke were excluded.
Although some features of the initial computed tomogram had highly significant associations with the presence of a cardiac source of embolism, the predictive value of these features for an embolic source was low.
Arginine vasopressin V1-antagonist and atrial natriuretic peptide reduce hemorrhagic brain edema in rats.
Authors: Rosenberg G A , Scremin O , Estrada E , Kyner W T 
Published: June 2011

Injection of arginine vasopressin into the cerebral ventricles in animals with brain injury increased brain water, whereas injection of atrial natriuretic peptide reduced water content. Therefore, to determine the role of endogenous arginine vasopressin in brain edema, we attempted to inhibit edema from a hemorrhagic lesion with an arginine vasopressin V1 receptor antagonist or atrial natriuretic peptide.
Adult Sprague-Dawley rats with hemorrhages induced by 0.4 IU bacterial collagenase were treated with 75 ng (n = 9) or 8 micrograms (n = 9) of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)Arg, 3.2 micrograms (n = 4) atrial natriuretic peptide injected intracerebrally, or 5 micrograms/kg per hour (n = 7) atrial natriuretic peptide intraperitoneally. They were compared with control groups injected with 0.4 IU collagenase only. Brain water and electrolytes were measured 24 hours later. Brain uptake of [14C]sucrose was measured 30 minutes after lesions were induced by 0.4 IU collagenase alone (n = 5) or after collagenase injection and 50 micrograms/kg per hour (n = 5) atrial natriuretic peptide injected intravenously.
The arginine vasopressin V1 receptor antagonist and atrial natriuretic peptide significantly (p < 0.05) reduced water and sodium contents in the posterior edematous regions. Brain uptake of [14C]sucrose was significantly reduced by intravenous atrial natriuretic peptide.
Antagonists to arginine vasopressin V1 receptors and atrial natriuretic peptide both significantly reduce hemorrhagic brain edema, and atrial natriuretic peptide appears to protect the blood-brain barrier.
Incidental brain lesions on magnetic resonance imaging and neurobehavioral functions in the apparently healthy elderly.
Authors: Matsubayashi K , Shimada K , Kawamoto A , Ozawa T 
Published: June 2011

Controversies exist whether incidental neuroradiological brain lesions in the elderly are associated with depressed neuropsychological function. To address this important issue in a cross-sectional study, we related brain lesions on magnetic resonance imaging to a variety of cognitive and neurobehavioral function tests in an independent, normal elderly population.
We studied 73 independent asymptomatic elderly individuals (mean +/- SD age 70 +/- 6 years) to determine the relations between degree of brain atrophy, location and number of "lacunes," and grade of periventricular hyperintense lesions with a variety of cognitive and neurobehavioral function scores.
We found that severity of neuroradiological changes increased while neuropsychological function scores declined with age. After adjustment for the effect of age, advanced periventricular hyperintensities, but not brain atrophy or patchy "lacunar" lesions, were associated with declines in all neuropsychological functions tested.
We conclude that incidental advanced periventricular diffuse or patchy white matter changes may play a role in the development of cognitive and neurobehavioral impairments in apparently normal elderly persons.
Mechanisms in lacunar infarction.
Authors: Horowitz D R , Tuhrim S , Weinberger J M , Rudolph S H 
Published: June 2011

Lacunes are thought to occur in patients with hypertension or diabetes mellitus as a result of small-vessel disease. This study evaluated the importance of other stroke mechanisms in a population of patients with lacunar infarction.
We evaluated 108 consecutive patients with a lacune in the lenticulostriate distribution for other stroke risk factors such as carotid and cardiac disease.
Hypertension was present in 68% of the patients and diabetes mellitus in 37%; both occurred in 28% and neither occurred in 23%. Noninvasive carotid studies identified atherosclerotic plaque as a possible embolic source in 23%. By previously established criteria, 18% were at high risk for cardioembolism. Of those with hypertension or diabetes mellitus, 36% were at risk for a carotid or cardiac embolus. Of those without hypertension or diabetes mellitus, 32% had a possible carotid or cardiac etiology.
The high incidence of carotid and cardiac disease in those with and without hypertension or diabetes mellitus suggests the importance of other stroke mechanisms in this population. Patients with lacunar infarction should therefore be evaluated for other causes of stroke that may be treatable.
Effects of public and professional education on reducing the delay in presentation and referral of stroke patients.
Authors: Alberts M J , Perry A , Dawson D V , Bertels C 
Published: June 2011

Several emerging stroke therapies require patients to be treated within several hours of symptom onset. Past studies have documented a significant delay between symptom onset and hospital presentation. As part of an experimental treatment study using tissue-type plasminogen activator, we began a multifaceted program of public and professional education to reduce the delay in presentation and referral of acute stroke patients.
The educational efforts focused on improving the recognition of stroke symptoms, the study enrollment criteria, and the need for rapid treatment of stroke patients. This program included 1) interviews on television and radio, 2) newspaper articles, 3) lectures to local and regional primary care and emergency department physicians, 4) mailings to several thousand local physicians, 5) having neurologists on-call for referrals 24 hrs/day, and 6) use of the Duke Life-Flight helicopter.
Since starting our program, 139 of 159 (86%) patients with cerebral infarction presented primarily to our were referred to our facility within 24 hours of symptom onset, compared with 70 of 187 (37%) before our educational efforts (p less than 0.00001). No significant change was seen in patients with intracerebral hemorrhage (23 of 30 +AD77%+BD within 24 hours after program, compared with 25 of 40 +AD63%+BD before educational efforts; p = 0.30).
These findings suggest that educational efforts aimed at the public and health professionals may increase recognition of stroke symptoms and reduce the delay in presentation and referral of stroke patients.
Ultrasonic evaluation of the site of carotid axis occlusion in patients with acute cardioembolic stroke.
Authors: Yasaka M , Omae T , Tsuchiya T , Yamaguchi T 
Published: June 2011

We performed the present study to determine whether the site of cardioembolic occlusion in the carotid axis could be identified by end-diastolic velocity measurements of the common carotid arteries.
Using duplex carotid ultrasonography, we measured the flow velocity in the common carotid arteries and calculated the side-to-side ratios of the end-diastolic velocity (ED ratio; the end-diastolic velocity of the nonaffected side divided by that of the affected side) in 46 patients with acute cardioembolic stroke. The velocity on the faster side was divided by the slower velocity to obtain the normal values of ED ratio in 30 controls. The ED ratios were compared with the angiographic findings, in which unilateral intracranial internal carotid artery occlusion was present in 20 patients (IC group), occlusion of the horizontal segment of the middle cerebral artery was present in 16 patients (M1 group), and branch occlusion of the middle cerebral artery was present in 10 patients (MBr group). The ED ratios of the control group were less than 1.3; those of the MBr group generally less than 1.3; the IC group greater than 4.0, except in two patients with severe cerebral edema; and those of the M1 group between 1.3 and 4.0. Therefore, the IC group was easily distinguished from the other groups by an ED ratio greater than or equal to 4.0, with an accuracy of 97%, and the M1 group by an ED ratio greater than or equal to 1.3 and less than 4.0, with an accuracy of 93%.
We found the ED ratio useful to identify internal carotid artery and middle cerebral artery occlusion in patients with cardioembolic stroke unless severe cerebral edema was present.