Posted 11 July 2004 - 04:58 AM
Hexacosanol
Exp Neurol. 1996 Apr;138(2):189-97.
Enhancement of mouse sciatic nerve regeneration by the long chain fatty alcohol, N-Hexacosanol.
Azzouz, M, Kenel PF, Warter J-M, Poindron P, Borg J. Universite Louis Pasteur, Centre de Recherches Pharmaceutiques, ILLKIRCH, France.
The purpose of the present study was to determine the effects of n-hexacosanol (hexa) on nerve regeneration. Hexa, a long chain fatty alcohol has been shown to possess neurotrophic properties on cultured neurons and to attenuate the degeneration of cholinergic neurons after injury. The effects of daily intraperitoneal injections of hexa (1 mg/kg) on regeneration of nerve fibers were studied in mice following a sciatic nerve crush. Measurement of axonal regeneration using the pinch test 7 days postlesion showed a 40% increase of the regeneration rate of sensory fibers in hexa-treated mice compared to controls (1.67 +/- 0.15 mm/day and 1.09 +/- 0.03 mm/day, respectively). The recovery of neuromuscular function was significantly improved, as shown by quantitative electromyography and and sensorimotor tests. Clinical signs of recovery evaluation with toe spreading reflex appeared earlier in hexa group than in control animals. Electrophysiological recordings were performed each 3 days during 34 days following nerve injury. Higher values of the compound muscle action potential (CMAP) were obtained in hexa-treated animals that correspond to an improved regeneration. Moreover, hexa induced a significantly faster regeneration rate (hexa: 2.87 +/- 0.15 mV/day; control: 2.00 +/- 0.06 mV/day), as measured by the slope of CMAP increase (44% enhancement). A morphometric analysis performed 7 days following crush showed an increased number of regenerating fibers, as well as increased diameter and thickness of the myelin in hexa-treated mice. Thus, hexa increased the regeneration of both sensory and motor axons in lesioned nerve, leading to an improved functional recovery.
J Neurosci Res. 1991 May;29(1):62-7.
The neurotrophic factor, n-hexacosanol, reduces the neuronal damage induced by the neurotoxin, kainic acid.
Borg J.
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 intraperitineal 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 exicotoxin-related human diseases.
Brain Res. 1990 Jun 4;518(1-2):295-8.
Peripheral administration of a long-chain fatty alcohol promotes septal cholinergic neurons survival after fimbria-fornix transection.
Borg J, Kesslak PJ, Cotman CW. Medafor, Schiltigheim, France.
Peripherally administered n-hexacosanol, a long-chain fatty alcohol, strongly attenuated the degeneration of cholinergic neurons in the medial septum and the vertical limb of the diagonal band of Broca following transection of their dorsal projection to the hippocampus by unilateral fimbria-fornix aspiration. The maintenance of AChE-positive neurons was particularly striking in the vertical limb of the diagonal band of Broca, where 83% of the neurons survived after two weeks of n-hexacosanol treatment compared to 51% in the non-treated animals. This compound has already been found to possess some neurotrophic activities on cultured neurons from rat cerebral cortex. But the present study is the first report of an in vivo neurotrophic influence exerted by an exogenously administered long-chain fatty alcohol. The low dosage needed and the peripheral administration of this compound may be of great advantage in the reduction of cell loss in some neurodegenerative disorders like Alzheimer's disease or stroke.
FEBS Lett. 1987 Mar 23;213(2):406-10.
Neurotrophic effect of naturally occurring long-chain fatty alcohols on cultured CNS neurons.
Borg J, Toazara J, Hietter H, Henry M, Schmitt G, Luu B.
A long-chain fatty alcohol,n-hexacosanol, that we have isolated from the Far-Eastern traditional medicinal plant, Hygrophila erecta, Hochr., is shown to promote the maturation of central neurons. Added at 500 nM to fetal rat brain neurons in culture, it increased both neurite outgrowth by a factor of 4-6 and the number of collaterals, especially in multipolar neurons. The biochemical differentiation of cultured neurons was also strikingly enhanced by this compound: it increased the protein content and almost doubled the activities of two neuron-specific enzymes, phosphate-activated glutaminase and neuron-specific enolase, by 92 and 78%, respectively. Extensive studies with several synthetic long-chain fatty alcohols showed that the neurotrophic activity was maximal for n-hexacosanol. It is suggested that some long-chain fatty alcohols with an appropriate length of hydrocarbon chain might play an important role in central neuron development.
