Neuroprotective properties of the novel antiepileptic drug levetiracetam in the rat middle cerebral artery occlusion model of focal cerebral ischemia

Abstract

Levetiracetam (LEV) is a new antiepileptic drug with a promising preclinical profile involving both anticonvulsant and antiepileptogenic effects in kindling models. The latter stimulated the present study to compare its neuroprotective properties with the potent and selective, non-competitive NMDA antagonist, MK-801, in the rat middle cerebral artery occlusion model. Twenty-four hours after a transient occlusion of 90 minutes the animals were sacrificed and infarct volume and lesion distribution were determined from stained coronal sections. LEV was administered by intraperitoneal (i.p.) bolus injections of 5.5, 11, 22 and 44 mg x kg(-1), 30 minutes before occlusion followed by a continuous 24 hour i.p. infusion of 1.25, 2.6, 5.1 and 10.2 mg x kg(-1) per hour, respectively. LEV administration did not alter body temperature but reduced the infarct volume by 33% (P< 0.05) at the highest dose tested. An i.p. bolus injection of 0.04, 0.12 and 0.4 mg x kg(-1) of MK-801 followed by continuous i.p. infusion of 0.036, 0.108 and 0.36 mg x kg(-1) per hour, reduced the infarct volume by 49, 51 and 74% (P< 0.05), respectively. However, only the highest dose of MK-801 induced a significant reduction in the infarct volume (P< 0.05) and this was associated with hypothermia. These results suggest that LEV possesses neuroprotective properties which may be relevant for its antiepileptogenic action.

Multiple Mechanisms Underlying the Neuroprotective Effects of Antiepileptic Drugs Against In Vitro Ischemia

“…22,23 The lack of neuroprotective effect by LEV is rather surprising. It has been shown, in fact, that this drug reduces the ischemia-induced brain damage in vivo 24 and is neuroprotective against kainate-induced toxicity. 25 Moreover, the present study, as well as previous works, 26,27 has shown that LEV reduces HVA Ca 2ϩ currents, one of the major target of putative neuroprotective therapies.…”

Seizures and Epilepsy After Ischemic Stroke

“…80,81 As demonstrated in laboratory animal studies of focal and global ischemia, antiepileptic drugs may also act as neuroprotectants. 82 For example, phenytoin, 83 benzodiazepines, 84 lamotrigine, [85][86][87][88] topiramate, 89 -91 levetiracetam, 92 and zonisamide 93 have neuroprotective properties and might, therefore, have beneficial effects when used to treat seizures in the setting of hyperacute stroke. However, there remain no clinical data proving this to be true, and the comparative risks and benefits of the different antiepileptic drugs have not been well studied in stroke patients.…”

Protective Effects of Systemic Piracetam Treatment on Testicular Torsion/Detorsion Damage in Rats: A Dose-Response Study

“…Histopathological changes were not observed in Group Piracetam, a nootropic drug, has been already used for neurological, neuropsychiatrical, and neurosurgerical disorders (6,7,(16)(17)(18). In conclusion, piracetam therapy increased antioxidant activity and decreased oxidative stress scores in testicular samples.…”

“…Piracetam is a nootropic agent used in neurological sciences because of its rheological, anti-thrombotic, and neuro-protective properties (6). After proving of its influence on improving micro-circulation, the area of usage for this drug extended (7).…”