THE NEUROTROPHIC FACTOR, NORMAL-HEXACOSANOL, REDUCES THE NEURONAL DAMAGE INDUCED BY THE NEUROTOXIN, KAINIC ACID

The long-chain fatty alcohol, n-hexacosanol, has been shown to possess neurotrophic properties in vitro on rat CNS cultures (Borg et al., 1987) and to promote the survival of septal cholinergic neurons after experimental axotomy (Borg et al., 1990). Long-chain alcohols have also been shown to be synthesized and metabolised by rat brain during development (Bishop and Hayra, 1981; Natarajan et al., 1984). The present study was undertaken in order to find out if a nonproteic neurotrophic factor like n-hexacosanol may be able to reduce the neuronal damages induced by the excitatory amino acid, kainic acid. When administered chronically by intraperitoneal injection, hexacosanol (1 mg/kg) protected the pyramidal neurons of the hippocampus from the neurotoxic degeneration induced by an intracerebroventricular infusion of kainic acid in rats; the extent of the damage was limited to a small part of the CA3 region. Morphometric analysis showed that 72% of the neurons that would have died following kainic acid injection were spared by hexacosanol. Moreover the increased locomotor activity induced by the neurotoxin was also inhibited by hexacosanol and the behavioral effect was statistically correlated to the extent of neuronal loss. The present study suggests a possible role for nonproteic neurotrophic compounds against neurotoxic damages on central neurons. Moreover the peripheral administration of hexacosanol may lead to a significant breakthrough in the treatment of excitotoxin-related human diseases.