Experimental neurology
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Experimental neurology · Nov 2004
Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy.
Excess ingestion of pyridoxine (vitamin B6) causes a severe sensory neuropathy in humans. The mechanism of action has not been fully elucidated, and studies of pyridoxine neuropathy in experimental animals have yielded disparate results. ⋯ The present study used design-based stereological techniques in conjunction with electrophysiological measures to quantify the morphological and physiological changes that occur in the DRG and the distal myelinated axons of the sciatic nerve following pyridoxine intoxication. This combined stereological and electrophysiological method demonstrates a general approach that could be used for assessing the correlation between pathophysiological and functional parameters in animal models of toxic neuropathy.
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Experimental neurology · Nov 2004
Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury.
Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). This immunohistochemical study determined the extent of AD-related changes in temporal cortex resected from individuals treated surgically for severe TBI. Antisera generated against Abeta species (total Abeta, Abeta(1-42), and Abeta(1-40)), the C-terminal of the Abeta precursor protein (APP), apolipoprotein E (apoE), and markers of neuron structure and degeneration (tau, ubiquitin, alpha-, beta-, and gamma-synuclein) were used to examine the extent of Abeta plaque deposition and neurodegenerative changes in 18 TBI subjects (ages 18-64 years). ⋯ Our results demonstrate a differential distribution and course of intra- and extra-cellular AD-like changes during the acute phase following severe TBI in humans. Abeta plaques and early evidence of neuronal degenerative changes can develop rapidly after TBI, while fully developed NFTs most likely result from more chronic disease- or injury-related processes. These observations lend further support to the hypothesis that head trauma significantly increases the risk of developing pathological and clinical symptoms of AD, and provide insight into the molecular mechanisms that initiate these pathological cascades very early during severe brain injury.
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Experimental neurology · Nov 2004
Bladder and urethral sphincter responses evoked by microstimulation of S2 sacral spinal cord in spinal cord intact and chronic spinal cord injured cats.
Urinary bladder and urethral sphincter responses evoked by bladder distention, ventral root stimulation, or microstimulation of S2 segment of the sacral spinal cord were investigated under alpha-chloralose anesthesia in cats with an intact spinal cord and in chronic spinal cord injured (SCI) cats 6-8 weeks after spinal cord transection at T9-T10 spinal segment. Both SCI and normal cats exhibited large amplitude reflex bladder contractions when the bladder was fully distended. SCI cats also exhibited hyperreflexic bladder contractions during filling and detrusor-sphincter dyssynergia during voiding, neither was observed in normal cats. ⋯ However, this stimulation evoked incomplete voiding due to either co-activation of the urethral sphincter or detrusor-sphincter dyssynergia. Stimulation in the S2 dorsal horn evoked large amplitude sphincter responses. The effectiveness of spinal cord microstimulation with a single electrode to induce prominent bladder and urethral sphincter responses in SCI animals demonstrates the potential for using microstimulation techniques to modulate lower urinary tract function in patients with neurogenic voiding dysfunctions.
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Experimental neurology · Nov 2004
Quantitative assessment of deficits and recovery of forelimb motor function after cervical spinal cord injury in mice.
A large proportion of spinal cord injuries (SCIs) in humans are at the cervical (C) level, but there are few tests to quantitatively assess forelimb motor function after cervical spinal cord injury in rodents. Here, we describe a simple and reliable technique for assessing forelimb grip strength over time. Female C57Bl/6 mice were trained on the Grip Strength Meter (GSM, TSE-Systems), then received a lateral hemisection of the spinal cord at level C5, C6, C7, or T1. ⋯ The ipsilateral forepaw exhibited no ability to grip until about 10-14 days postlesion, at which time grip reappeared and strength then recovered over a period of a few days to a level that was about 50% of preinjury levels. Grip strength was minimally and transiently affected by hemisection at T1. The grip strength analysis provides a convenient, quantitative measure of the loss and recovery of forelimb function after cervical injury.
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Experimental neurology · Nov 2004
Neuroprotection in the rat lateral fluid percussion model of traumatic brain injury by SNX-185, an N-type voltage-gated calcium channel blocker.
Overload of intracellular calcium ([Ca(2+)](i)) following traumatic brain injury (TBI) has been implicated in the pathogenesis of neuronal injury and death. Voltage-gated calcium channels (VGCCs) provide one of the major sources of Ca(2+) entry into cells. Therefore, the potential neuroprotective activity of SNX-185, a specific N-type VGCC blocker, was tested in rats using the lateral fluid percussion (LFP) model of TBI. ⋯ Direct injection of SNX-185 into the CA2-3 region of the hippocampus reduced neuronal injury 24 h after TBI and increased neuronal survival at 42 days at each of the three drug concentrations. Behavioral outcome in both the beam walk and Morris water maze were also improved by SNX-185, with 100 and 200 pmol, but not 50 pmol SNX-185 providing neuroprotection. These data support previous studies demonstrating substantial neuroprotection after TBI by treatment with N-type VGCC blockers.