Diazepam does not reduce infarct size in rats subjected to transient occlusion of the middle cerebral artery when normothermia is maintained.

ABSTRACT

Activation of the gamma-amino butyric acid (GABA)-ergic system might protect against the damage that occurs after cerebral ischaemia. We examined this hypothesis by administering diazepam to rats subjected to transient middle cerebral artery occlusion (MCAO) using the intraluminal thread method. Diffusion MRI (DWI) and perfusion imaging (PI) were acquired during MCAO to assess brain tissue status and haemodynamics, respectively. Rats were intraperitoneally injected with either 10 mg kg(-1) diazepam (n = 5) or vehicle (n = 5) both 30 min and 90 min after the onset of MCAO. To exclude the possibility that neuroprotection was due to the hypothermic action of the drug, body temperature was maintained at 37-38 degrees C for up to 7 h postischaemia with a feed-back controlled thermoregulatory unit. Infarct volumes quantified 2 days after MCAO from T(2)-weighted images were similar in ischaemic control rats and in ischaemic rats treated with diazepam. We conclude that diazepam-induced enhancement of GABA(A) activity does not effectively protect against neuronal damage that occurs after transient MCAO in normothermic rats.