PROTECTION OF NEUROLOGICAL FUNCTION IN STROKE MODELS AND NEUROPROTECTIVE PROPERTIES OF LUBELUZOLE

Lubeluzole, the S-isomer of a novel difluorobenzothiazole, is a neurop rotective compound aimed at the treatment of acute ischaemic stroke. I n a photochemical stroke model in rats, in which a neurological test w as designed that is also relevant to other stroke models, intravenous posttreatment with lubeluzole stereoselectively rescues sensorimotor f unction (time window of 6 h) and reduces infarct size. Posttreatment w ith lubeluzole also reduces infarct size after middle cerebral artery occlusion in rats, attenuates delayed neuronal death after global isch aemia, and may also act on mechanisms of cerebral oedema. The compound normalizes peri-infarct neuronal excitability and blocks the rise of peri-infarct extracellular concentration of glutamate. Lubeluzole down regulates the nitric oxide synthase (NOS) pathway leading to neurotoxi city and neuronal death. NOS pathway modulation may contribute to the neuroprotective properties of lubeluzole.