Korean J Anesthesiol.  2010 Feb;58(2):184-190. 10.4097/kjae.2010.58.2.184.

The effects of gabapentin pretreatment on brain injury induced by focal cerebral ischemia/reperfusion in the rat

• Kim YK
• Leem JG
• Sim JY
• Jeong SM
• Joung KW

• KMID: 2092275
• DOI: http://doi.org/10.4097/kjae.2010.58.2.184

Abstract

BACKGROUND
Experimental studies have shown that gabapentin can reduce neuronal injury in the setting of cerebral ischemia, but the mechanisms have not yet been clearly determined. This study was conducted to determine whether gabapentin pretreatment altered expression levels of heat shock protein 70 and reduced acute phase neuronal injury in rats subjected to transient focal cerebral ischemia/reperfusion. METHODS: Forty male Sprague-Dawley rats (260-300 g) were randomly assigned to one of four groups (saline-treated, or 0.1, 0.5, or 5 mg/kg gabapentin group). In all animals, focal cerebral ischemia was induced by intraluminal middle cerebral artery occlusion for 1 hour. The animals of the gabapentin groups were pretreated with a single intravenous administration of gabapentin 20 minutes before ischemic insults. The infarct volume, brain edema and motor behavior deficits were analyzed 24 hours after ischemic insult. Caspase-3-reactive cells and cells showing Hsp70 activity were counted in the caudoputamen and fronto-parietal cortex. RESULTS: The infarction ratio was significantly decreased in the 5 mg/kg gabapentin group (P < 0.05) and brain edema ratios were significantly reduced in the 0.1 mg/kg, 0.5 mg/kg, and 5 mg/kg gabapentin groups 24 hours after ischemia/reperfusion injury (P < 0.05). There were more Hsp70-reactive cells in the 5 mg/kg gabapentin group than in the saline group in both the caudoputamen and fronto-parietal cortex (P < 0.05). CONCLUSIONS: These results indicate that gabapentin may have a neuroprotective effect and can reduce early neuronal injury caused by focal cerebral ischemia/reperfusion; this may be mediated by expression of Hsp70. However, gabapentin pretreatment did not prevent caspase-dependent apoptosis.

Keyword

Caspase-3; Focal cerebral ischemia/reperfusion; Gabapentin; Heat shock protein 70; Rat

MeSH Terms

Administration, Intravenous
Amines
Animals
Apoptosis
Brain
Brain Edema
Brain Injuries
Brain Ischemia
Caspase 3
Cyclohexanecarboxylic Acids
gamma-Aminobutyric Acid
HSP70 Heat-Shock Proteins
Humans
Infarction
Infarction, Middle Cerebral Artery
Male
Neurons
Neuroprotective Agents
Rats
Rats, Sprague-Dawley
Amines
Caspase 3
Cyclohexanecarboxylic Acids
HSP70 Heat-Shock Proteins
Neuroprotective Agents
gamma-Aminobutyric Acid