Neuroprotective Effects of ACTH4-10PRO8-GLY9-PRO10

Study Overview
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Brief Summary
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The compound ACTH4-10Pro8-Gly9-Pro10 is a synthetic analog molecule of an adrenocorticotropic hormone (ACTH) short fragment. That is free from hormonal effects and has neuromodulatory effects. We investigate the neuroprotective effects of ACTH4-10Pro8-Gly9-Pro10 can lessen neurotoxicity against ketamine in neonatal rats by looking at BDNF expression in the cortex and hippocampus tissue as well as BDNF blood levels.

Detailed Description
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The compound ACTH4-10Pro8-Gly9-Pro10 is a synthetic analog molecule of a short fragment of adrenocorticotropic hormone (ACTH). It is free from hormonal effects and has neuromodulatory effects. The immune-modulating and neurotrophic activity of the drug were shown to balance the state of anti-inflammatory and trophic factors (IL-IO, TNF-a, TGF-Pl, BDNF, NGF) over proinflammatory factors (IL-Ip, IL-8, CRP, LE) to increase the anti-apoptotic defense (Bcl-2 elevation), as well as to reduce the peroxidation process (increased SOD activity). ACTH4-10Pro8-Gly9-Pro10 also has neuromodulator characteristics to function as a neuroprotector in inhibiting the apoptotic process. Modulation by ACTH4-10Pro8-Gly9-Pro10 will increase the levels of BDNF thereby inhibiting the process of apoptosis. Based on research by Gusev and Skvortsova, ischemic stroke patients who were given ACTH4-10Pro8-Gly9-Pro10 showed increased levels of BDNF, decreased mortality, and reduced length of stay. Based on the description above, the researcher was interested in analyzing the effect of the administration of ACTH4-10Pro8-Gly9-Pro10 on ketamine neurotoxicity in neonatal rats by assessing the level of BDNF.

Official Title
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Neuroprotective Effects of ACTH4-10PRO8-GLY9-PRO10 on The Ketamine-Induced Neurotoxicity In Neonatal Rats: Increased BDNF Expression And BDNF Serum Concentrations

Conditions
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Ketamine-Induced Neurotoxicity

Intervention / Treatment
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* Drug: ACTH4-10Pro8-Gly9-Pro10
* Drug: Ketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rattus norvegicus rats Male, seven days old, weighing 15-20 grams Spraque-Dawley strain, obtained from the Experimental Animal Care Unit Exclusion Criteria: Animals that behave aggressively in observation by attacking other groups

Ages Eligible for Study
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Minimum Age: 7 Days
Maximum Age: 7 Days

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACTH4-10PRO8-GLY9-PRO10<br>The compound ACTH4-10Pro8-Gly9-Pro10 is a synthetic analog molecule of a short fragment of adrenocorticotropic hormone (ACTH). It is free from hormonal effects and has neuromodulatory effects. | Drug: ACTH4-10Pro8-Gly9-Pro10<br>* ACTH4-10Pro8-Gly9-Pro10 also has neuromodulator characteristics to function as a neuroprotector in inhibiting the apoptotic process. Modulation by ACTH4-10Pro8-Gly9-Pro10 will increase the levels of BDNF thereby inhibiting the process of apoptosis<br>|
| Active Comparator: ketamine 40 mg/kg BW subcutaneously<br>ketamine results in impaired brain function associated with neuroapoptosis injury in the immature brain. | Drug: Ketamine<br>* negative-positive control (ketamine 40 mg/kg BW subcutaneously)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BDNF Expression | a protein that, in humans, is encoded by the BDNF gene | On 6 hours after the study drug dose | 
| BDNF Serum Concentrations | a protein that, in humans, is encoded by the BDNF gene | On 6 hours after the study drug dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACTH4-10Pro8-Gly9-Pro10, BDNF, ketamine-induced neurotoxicity, apoptosis