Effectiveness of GK-2, a Nerve Growth Factor Mimetic, in Preventing Post-Resuscitation Changes in the Brain

Abstract

Neurological status was assessed and the numbers of neurons per 1 mm in pyramidal neuronal layer length in CA1 and CA4 hippocampal fields and cerebellar Purkinje cells were evaluated in albino male rats on post-resuscitation day 14 after 12-min cardiac arrest. Intraperitoneal administration of GK-2 (1 mg/kg 30 min after resuscitation and within the next 3 days with an interval of 24 h) accelerated neurological recovery of the animals, sharply reduced the intensity of cerebellar Purkinje cell death, and prevented loss of pyramidal neurons in the hippocampus. These results show the effectiveness of systemic administration of the nerve growth factor mimetic GK-2 in improving structural and functional state of the brain in the post-resuscitation period. This opens new prospects of its use for prevention and correction of post-hypoxic encephalopathy.

A New Dipeptide H-MGL Partially Ameliorates Memory Impairment in an STZ-Induced Alzheimer Model in Male Rats

“…This suggests that the dosage may not be optimal. In contrast to our findings, Zarzhetskii et al reported that the administration of a dipeptide at a dosage of 1 mg/kg exhibited potential efficacy in the treatment of brain injury subsequent to resuscitation (21). In this way, as we used a higher dosage of the dipeptide (2 mg/kg), we observed that the group receiving 2 mg/kg H-MGL demonstrated improved cognitive function by efficiently locating the invisible platform similar to the sham group.…”

Low‐molecular mimetics of nerve growth factor and brain‐derived neurotrophic factor: Design and pharmacological properties

“…NGF, nerve growth factor postresuscitative period (14 days after surgery), GK-2 completely prevented the death of hippocampal neurons and approximately halved the death of cerebellum Purkinje cells. 93 The dipeptide GK-2 revealed antiparkinsonian effects. 94 In a model of haloperidol catalepsy in rats, GK-2 reduced the catalepsy severity by 80%-90% at ip administration at doses of 0.01-5 mg/kg 24 h before haloperidol and remained active at oral administration at doses of 5 and 10 mg/kg.…”

“…In a model of complete global ischemia in rats caused by cardiac arrest with further resuscitation, GK‐2 (0.5 mg/kg ip) when administered 30 min after surgery and then every 24 h for next 3 days accelerated the restoration of the neurological status of animals and prevented damage to Purkinje cells of the cerebellum and hippocampal pyramidal neurons in the early postresuscitative period (7 days after surgery). In the long‐term postresuscitative period (14 days after surgery), GK‐2 completely prevented the death of hippocampal neurons and approximately halved the death of cerebellum Purkinje cells 93 …”