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

Abstract

BackgroundExperimental 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.MethodsForty 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.ResultsThe 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).ConclusionsThese 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.

Aβ and Aδ but not C-fibres are involved in stroke related pain and allodynia: an experimental study in mice

“…Potential mechanisms that may contribute to central sensitization include increased N‐methyl‐ d ‐aspartic acid (NMDA) and α ‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate (AMPA) receptor‐mediated excitatory synaptic transmission in the dorsal horn; a decrease in γ ‐aminobutyric acid (GABA) and glycine receptor‐mediated inhibitory synaptic transmission; an increase in descending facilitation; [31–33] it is possible these mechanism may be involved in the development of post‐stroke allodynia observed in this study. It is reported that the increase of synaptic glutamate or excess influx of calcium ion into neuronal cells following NMDA‐receptor activation significantly exacerbated the development of infarction [34,35] . As described above, similar molecules are known to be involved in the mechanism of development of pain [25,36] .…”

“…It is reported that the increase of synaptic glutamate or excess influx of calcium ion into neuronal cells following NMDA-receptor activation significantly exacerbated the development of infarction. [34,35] As described above, similar molecules are known to be involved in the mechanism of development of pain. [25,36] Thus, some drugs such as NMDA-receptor antagonists and calcium channel blockers would be effective in inhibiting the development of infarction as well as development of post-stroke allodynia.…”

Research Article Expression of miR-15b, miR-29b, miR-219 and miR-222 microRNAs in rats with focal cerebral ischemia submitted to physical exercise

“…Most strokes are ischemic and cause injury to a specific region of the brain by restriction of blood flow (Dhiraj et al, 2013). The incidence of stroke in the United States affects between 500,000 and 750,000 people annually, especially those over 65 years old (Kim et al, 2010). There are several important risk factors that contribute to cerebral ischemia, among them are hypertension, smoking, sedentary lifestyle and obesity (Bronner et al, 1995).…”

Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats

“…[11] Gabapentin, which has entered into clinical use as an adjuvant anticonvulsant drug in the treatment of partial seizures in 1993, is widely used for neuropathic pain, migraine, and spasticity today. [12][13][14] The antinociceptive, anticonvulsant, anxiolytic, and neuroprotective effects of gabapentin have been shown in various animal models. [15] It has been suggested that the neuroprotective effects of gabapentin may be related to changes in glutamate synthesis and metabolism.…”

“…[15] It has been suggested that the neuroprotective effects of gabapentin may be related to changes in glutamate synthesis and metabolism. [13,16] There are many studies investigating its neuroprotective effects in cerebral ischemia, cerebral trauma, spinal cord trauma, and peripheral nerve injury.…”