Behavioral effect of dipeptide NGF mimetic GK-2 in an in vivo model of rat traumatic brain injury and its neuroprotective and regenerative properties in vitro

Abstract

A protective behavioral effect of a nerve growth factor dipeptide mimetic GK-2 in the model of open focal trauma of rat brain sensorimotor cortex and its antioxidative and regenerative properties in cultures of rat cerebellar granule cells and mouse embryonal spinal ganglion, respectively, were studied. Intraperitoneal injections of GK-2 (1 mg/kg) for 5 days daily after traumatic brain injury improved significantly motor function of limbs. Moreover, supplementation the incubation medium with GK-2 (0.5–1.5 mg/l) decreased neuronal death induced by H₂O₂ in cerebellar granule cell cultures and stimulated neurite outgrowth from cultured mouse embryonal spinal ganglia. Our results suggest that GK-2 exhibits pronounced positive behavioral effect in vivo as well as neuroprotective and regenerative effects in vitro, and that these neuroprotective properties probably associated with cell survival but not with cell differentiation pathway.

KEYWORDS:

• traumatic brain injury
• neuroprotection
• dipeptide mimetic of nerve growth factor
• GK-2
• cerebellar granule cultures