Experimental neurology
-
Experimental neurology · Jun 1996
Restraint reduces formalin-test pain but the effect is not influenced by lesions of the hypothalamic paraventricular nucleus.
Previous research indicates that the paraventricular nucleus of the hypothalamus (PVN) plays an important role in the development of stress-induced analgesia (SIA). Research implicating the PVN in SIA has generally employed the cold-water swim as the stressor and a phasic pain test, such as the tail-flick test, as the pain model. The present study, using the formalin test for tonic pain, investigated the effect of PVN lesions on (1) tonic pain responses and (2) SIA caused by 30 min of restraint. ⋯ The short-term SIA is reflected as a decrease in paw licking, whereas the long-term SIA is reflected as a decrease in paw elevation. In addition, PVN lesions failed to alter SIA during both phases of the formalin test. The differential effect of restraint on pain responses during the two phases of the formalin test and the lack of effect of PVN lesions on SIA for tonic pain suggest that stress engages multiple endogenous pain inhibitory systems.
-
Experimental neurology · Mar 1996
Differential trophic effects of basic fibroblast growth factor, insulin-like growth factor-1, and neurotrophin-3 on striatal neurons in culture.
We have examined the trophic effects of basic fibroblast growth factor (bFGF), truncated insulin-like growth factor-1 (tIGF), and neurotrophin-3 (NT-3) on embryonic striatal neurons grown under serum-free culture conditions. Striatal neurons were identified using immunocytochemistry for dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32). In our serum-free striatal cultures, the survival and the development of DARPP-32- containing neurons were dependent on initial plating density: relatively high density cultures yielded disproportionately increased number of harvested DARPP-32- positive neurons. ⋯ There was no alteration of the morphology of this neuronal population in bFGF-treated cultures. All of these growth factors were seen to be approximately equally efficient at protecting striatal neurons from N-methyl-D- aspartate-induced excitotoxicity. These data indicate that bFGF, tIGF-1, and NT3 exert different trophic activities on striatal neurons in vitro and suggest that these growth factors might also be involved in the regulation of neuronal development and maintenance in the striatum.
-
Experimental neurology · Jan 1996
Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor, and noradrenergic neurites after adult spinal cord injury.
Several neurotrophic factors have been identified that influence neuronal populations during central nervous system development, maturation, and senescence. To examine the responsiveness of the intact and the lesioned adult mammalian spinal cord to neurotrophic factors, primary rat fibroblasts were genetically modified to produce and secrete human nerve growth factor (NGF). These NGF-producing cells were then grafted to nonlesioned or lesioned adult rat spinal cords for periods of up to 1 year in vivo. ⋯ Equally robust growth of sensory and noradrenergic neurites was observed in the lesioned spinal cord; in addition, partial sprouting of local motor neurites was elicited in the lesioned spinal cord. Thus, multiple neuritic populations of the adult spinal cord respond to neurotrophic factors by extending neurites, and this responsiveness is maintained and extended after major injury. Nerve growth factor delivered by somatic gene transfer may be a useful means of promoting axon regrowth in the injured spinal cord.
-
Experimental neurology · May 1995
Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol.
Taxol, a natural extract with antineoplastic properties, is known to be neurotoxic in humans. Its neurotoxicity after systemic administration, however, has never been studied in detail at the morphological level in humans and in animals. In this study we administered taxol intraperitoneally to female Wistar rats and we performed an extended neurophysiological and morphological examination of the peripheral nerves, dorsal root ganglia, spinal rootlets, and spinal cord. ⋯ The most impressive change induced by systemic taxol administration was intraaxonal neurotubule accumulation. Schwann cells showed signs of "activation" but clear demyelination was not observed. We conclude that with the use of this model it is possible to induce a peripheral neuropathy in the Wistar rat which resembles that reported in humans and which can, therefore, be used to better understand the basic mechanism(s) of taxol toxicity and to evaluate protective strategies in an attempt to reduce it.
-
Experimental neurology · Apr 1995
The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury.
Substantial residual neurological function may persist after spinal cord injury (SCI) with survival of as few as 5-10% of the original number of axons. A detailed understanding of the relationships among the severity of injury, the number and origin of surviving axons at the injury site, and the extent of neurological recovery after SCI is of importance in understanding the pathophysiology of SCI and in designing treatment strategies. In the present study, these relationships were examined in rats with graded severity of clip compression injury of the cord at T1. ⋯ The inclined plane scores varied as a negative linear function of the closing force of the clip used to inflict SCI (r = -0.93; P < 0.0001). The mean axon count was 367,000 +/- 59,000 in normal rats and decreased as a negative exponential function of injury force (r = -0.92; P < 0.0001). As well, SCI caused preferential destruction of large axons as reflected by the change in mean axon diameter from 1.74 +/- 0.06 microns in normal cords to 1.46 +/- 0.04 microns in injured cords (pooled mean for all injuries).(ABSTRACT TRUNCATED AT 250 WORDS)