Cerebro-protective effects of ENA713, a novel acetylcholinesterase inhibitor, in closed head injury in the rat

Yun Chen, Esther Shohami, Roman Bass, Marta Weinstock*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Focal ischemic brain damage and diffuse brain swelling occur in severe cases of traumatic head injury. Ischemia decreases brain acetylcholine (ACh) levels and head trauma upregulates acetylcholinesterase (AChE) in experimental animal models. The present study determined whether a brain- selective AChE inhibitor, ENA713, given once, up to 2 h after closed head injury (CHI) could reduce the vasogenic edema and accelerate recovery from neurological deficits induced by the injury in rats. ENA713 1-5 mg/kg produced a dose-related inhibition of AChE ranging from 40-85% in the cortex and hippocampus. Doses of 1, 2 and 5 mg/kg, significantly reduced the motor and neurological deficits and speeded recovery, as indicated by measurements made 7 and 14 days after injury. The two larger doses were still effective when injected 1 or 2 h after CHI. The acceleration by ENA713 of recovery of motor function was independent of its reduction in body temperature and was prevented by the simultaneous injection of mecamylamine (2.5 mg/kg), but not by scopolamine (0.2 or 1 mg/kg). Edema in the contused hemisphere (24 h after injury) and disruption of the blood brain barrier (4 h after injury) were significantly reduced (about 50%) by doses of 2 and 5 mg/kg, but not by 1 mg/kg. The data support the hypothesis that ENA713 exerts a neuroprotective effect in brain injury by preventing the decrease in cholinergic activity in cerebral vessels and in neurones.

Original languageEnglish
Pages (from-to)18-24
Number of pages7
JournalBrain Research
Volume784
Issue number1-2
DOIs
StatePublished - 16 Feb 1998

Keywords

  • Acetylcholinesterase inhibitor
  • Blood-brain barrier
  • Brain edema
  • Closed-head injury
  • Neurological deficit
  • Rat

Fingerprint

Dive into the research topics of 'Cerebro-protective effects of ENA713, a novel acetylcholinesterase inhibitor, in closed head injury in the rat'. Together they form a unique fingerprint.

Cite this