J Korean Soc Endocrinol.  2001 Feb;16(1):26-38.

The Neuroprotective Effect of Growth Hormone on Neuronal Injury of Brain in Pilocarpine induced Status Epilepticus

• An RZ
• Yu JH
• Song KS

Abstract

BACKGROUND: Several growth factors, including growth hormone (GH) and Insulin like growth factor-I, have been reported to have a neuroprotective effect in experimental models of hypoxic ischemia. This study is aimed at assessing the clinical significance of growth hormone for neuroprotection in status epilepticus induced neuronal cell deaths.
METHODS
Pilocarpine induced status epilepticus (SE) was studied in rats (male, Sprague-Dawley). Rats were divided into pre- or post-treatment groups that had either a low (5 U/kg/day) or high (10 U/kg/day) dose of recombinant human GH (Eutropin, LGCI, Korea), and then subdivided into 24 hour, 72 hour and 1 week groups. This was done in the pretreatment groups for 5 days before SE and in the post-treatment groups for 5 days after 2 hrs of SE injection, after SE, the GH was daily injected via intraperitoneal route. Status epilepticus was induced by pilocarpine (360 mg/kg) with scoplamine (1 mg/kg) 30 minutes before pilocarpine injection using a stereotaxic instrument and EEG monitoring. Rats were killed at 24 and 72 hours after the SE in the pretreatment groups and at 1 week after the SE in the post-treatment groups for pathology studies. Neuronal injuries in the rat brain were studied by Hematoxylin & Eosin stain and the TUNEL method.
RESULTS
Neuronal necrosis was found in the hippocampal CA1 and CA3 regions in all experimenatal groups after SE, and was more severe in the CA3 region. Apoptosis was found only in the pre-GH treated group and there were TUNEL-positive and morphologically necrotic cells in the hippocampal CA1 and CA3 regions at 72 hours after SE. Neuronal necrosis and apoptosis were significantly decreased in the high dose GH treated groups (p<0.05) compare to controlsd, but not in the low dose GH hormone treated groups (p>0.05).
CONCLUSION
Growth hormone has a neuroprotective effect in neuronal cell death (necrosis and apoptosis) that is caused by pilocarpine induced status epilepticus in a dose dependent manner and prevents the activation of apoptosis by SE in neurons which eventually become necrotic.

MeSH Terms

Animals
Apoptosis
Brain*
Cell Death
Electroencephalography
Eosine Yellowish-(YS)
Growth Hormone*
Hematoxylin
Humans
In Situ Nick-End Labeling
Insulin
Intercellular Signaling Peptides and Proteins
Ischemia
Models, Theoretical
Necrosis
Neurons*
Neuroprotective Agents*
Pathology
Pilocarpine*
Rats
Status Epilepticus*
Eosine Yellowish-(YS)
Growth Hormone
Hematoxylin
Insulin
Intercellular Signaling Peptides and Proteins
Neuroprotective Agents
Pilocarpine