[Action of naftidrofuryl in cerebral neovascularization after cortical lesion in rats]. / Action du naftidrofuryl sur la néovascularisation cérébrale après lésion corticale chez le rat.

In this study, naftidrofuryl's action on vascular network regeneration is evaluated after cortical lesion produced by suction. The vascular reaction was analyzed in the region of the damaged cortex and the corresponding contralateral cortex. Comparison of results by variance analysis confirms that the effect of treatment is highly significant (p = 0.008). The results thus obtained show that post-lesion angiogenesis is facilitated and that capacities of post-lesion cerebral function regeneration could also be improved.

[Experimental approach to manifestations of senile dementia]. / Approche expérimentale des manifestations de la démence sénile.

Similar alterations in the neuronal cytoskeleton (paired helical filaments) and modifications in the molecular forms of acetylcholinesterase (specific decrease in the G4 form) have been detected in the elderly rat as well as in patients suffering from SDAT. These observations challenge the specificity of some manifestations of dementia to the human species and provide new opportunities to study these alterations using rat peripheral nervous system as an experimental model.

Reduced axonal transport of the G4 molecular form of acetylcholinesterase in the rat sciatic nerve during aging.

Aging in the sciatic nerve of the rat is characterized by various alterations, mainly cytoskeletal impairment, the presence of residual bodies and glycogen deposits, and axonal dystrophies. These alterations could form a mechanical blockade in the axoplasm and disturb the axoplasmic transports. However, morphometric studies on the fiber distribution indicate that the increase of the axoplasmic compartment during aging could obviate this mechanical blockade. Analysis of the axoplasmic transport, using acetylcholinesterase (AChE) molecular forms as markers, demonstrates a reduction in the total AChE flow rate, which is entirely accounted for by a significant bidirectional 40-60% decrease in the rapid axonal transport of the G4 molecular form. However, the slow axoplasmic flow of G1 + G2 forms, as well as the rapid transport of the A12 form of AChE, remain unchanged. Our results support the hypothesis that the alterations observed in aged nerves might be related either to the impairment in the rapid transport of specific factor(s) or to modified exchanges between rapidly transported and stationary material along the nerves, rather than to a general defect in the axonal transport mechanisms themselves.

[Study of the peripheral nerve fibers during aging in the rat]. / Etude des fibres nerveuses périphériques au cours du vieillissement chez le rat.

An histological study of the peripheral nervous fibres has been performed at various anatomical levels during aging: the spinal ganglion, the dorsal and the ventral nerve roots, the spinal and the sciatic nerves. During aging the various alterations occurring in a peripheral nerve can be summarized as following. In the myelinated fibres, the axoplasm was progressively invaded by several inclusions: glycogen granules, granulo-filamentous bodies and lipofuscins. The crystalloid networks arising from the cytoskeleton were mainly localised in the intraganglionic fibres. Among the axoplasmic organelles, the mitochondria were the most affected. The myelinic sheath split, became dystrophic and then was totally disrupted. The inner schwann cell compartment was invaded by several inclusions like Hirano bodies and dense residual deposits. Further, macrophages phagocytosed the axon and the myelin sheath. In the non-myelinated fibres, the alterations were less important and less precocious. When these results are analysed from a chronological point of view it is established that the alterations appear at the same time in each observed level but their amount differ from each other. In the 24-month-old-rats, the ventral root and the sciatic nerve present many dystrophies whereas in the spinal ganglion and in the dorsal root they are less numerous. From these results, it can be suspected that the motor fibres are more vulnerable during aging. Moreover, the myelinated fibres of large diameter are the first affected. Furthermore, only the ventral root and the sciatic nerve show typical regeneration pictures at 32 months.

The abilities of the rat brain to sustain the survival of implanted or cultured embryonic dorsal root ganglion neurons depend on the selected region.

The purpose of the present study was to examine the regional distribution of trophic activity in the lesioned adult rat brain on implanted peripheral neurons as target cells. Embryonic dorsal root ganglia (DRG) were implanted into selected regions of previously lesioned adult rat brains. The survival of these neurons was quantified after thirty days. In another experiment embryonic DRG neurons were cultured for 24 h together with tissue extracts of the same lesioned brain regions and the neuronal survival was estimated. We report here that all the tested regions, i.e. the occipital, parietal and frontal cortex, the hippocampus and the striatum, exert a trophic effect on embryonic DRG neurons both 'in vivo' and 'in vitro'. This effect is twice as high in the hippocampus as in the striatum, the other cortical regions showing intermediate values. The in vitro results are qualitatively the same as the in vivo results.

Transplantation of human cortex with Alzheimer's disease into rat occipital cortex; a model for the study of Alzheimer disease.

Senile dementia of the Alzheimer type (SDAT) is a major problem in the human senescent population. As this pathology cannot be reproduced in animals, research into its development is greatly impeded. The technique of implantation of the nervous tissue has been utilized in order to establish an animal model and to test the possible existence of a transmissible agent. When human temporal cortex with Alzheimer's disease is implanted in the occipital cortex of 7-week-old rats, human cerebral tissue containing abundant tangles induces in the receiver cortex a reactive fibrous gliosis. In the processes of the astrocytes, twisted filaments are evident among bundles of normal filaments. These alterations could be induced by the metabolising of abnormal filament subunits or by some infectious agent introduced by the implant.

Paired helical filaments in spinal ganglion neurons of elderly rats.

Ultrastructural study of spinal ganglion neurons in elderly rats (aged from 24 to 32 months) allowed the observation of spontaneously occurring paired helical filaments (PHFs). On the basis of this finding the rat may provide an animal model for the study of the morphogenesis and nature of the PHFs which are characteristic of human senile dementia of the Alzheimer type.

[Labeling cerebral activity with 3H-deoxyglucose after milacemide administration in the rat]. / Marquage de l'activité cérébrale par le 3H-déoxyglucose après administration de la milacémide chez le rat.

Milacemide (2-n-pentylaminoacetamide . HCl) is an anti-epileptic which improves the mood, vigilance and sociability of treated patients. By metabolic charting with radioactive deoxyglucose it is possible to estimate local consumption of glucose in the various regions of the brain in rats treated with milacemide in comparison with rats treated with a placebo. It would seem that milacemide exerts an appreciable activating effect principally on pathways with sensory functions. The activation of the metabolism of cerebral energy in these regions may explain the behavioural improvements observed in the rat and in the first clinical trials in man.