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Results for “selective vulnerability”

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PubMed1993

Acidic foci within the ischemic penumbra of the New Zealand white rabbit.

BACKGROUND AND PURPOSE: In vivo panoramic imaging of reduced nicotinamide adenine dinucleotide (NADH), intracellular brain pH (pHi), and cortical blood flow was used to characterize the ischemic penumbra during focal ischemia. During global ischemia, hypoxia, and status epilepticus, the development of cortical acidic foci has been observed. The hypothesis tested was that during focal ischemia, acidic foci develop, which may lead to recruitment of the ischemic penumbra into infarction. METHODS: Five fasted New Zealand White rabbits underwent middle cerebral artery (MCA) occlusion under 1.5% halothane anesthesia through a retro-orbital approach, and five animals served as controls. Brain pHi and cerebral blood flow were measured with in vivo umbelliferone fluorescence. RESULTS: Baseline brain pHi was 6.98 +/- 0.05, whereas cortical blood flow and NADH fluorescence measured 52.2 +/- 8.7 mL/100 g per minute and 35.5 +/- 3.7 gray-scale units, respectively. Fifteen minutes after MCA occlusion, overall brain pHi and cortical blood flow of the ischemic penumbra measured 6.61 +/- 0.06 and 31.9 +/- 9.2 mL/100 g per minute. Over 3 hours there was normalization of pHi in the majority of the penumbra due to increases in cortical blood flow. Within the ischemic penumbra acidic foci developed with an initial pHi of 6.35 +/- 0.09 and cortical blood flow of 18.0 +/- 5.7 mL/100 g per minute. These foci remained acidic with increased NADH fluorescence despite being surrounded by cortex that was recovering from ischemia. On light microscopy, these acidic foci had a mixed pattern of neuronal injury. CONCLUSIONS: Within the ischemic penumbra, acidic foci develop that do not follow a vascular distribution and have microscopic evidence of ischemic neuronal injury. This suggests that there is a cortical selective vulnerability regarding pHi regulation and these acidic foci may lead to recruitment of the ischemic penumbra into infarction.

Acidosis↗

PubMed1993

Reversed alterations of hippocampal parvalbumin and protein kinase C-gamma immunoreactivity after stroke in spontaneously hypertensive stroke-prone rats.

BACKGROUND AND PURPOSE: Aging spontaneously hypertensive stroke-prone rats (SHR-SP) were previously shown to develop neocortical strokes. Because the hippocampal CA1 is selectively vulnerable to abnormal brain perfusion, the neuropathological effects of spontaneous strokes were investigated on specific neurochemical alterations in two major cell types of the hippocampal CA1 in SHR-SP. METHODS: The immunoreactivity for the gamma-isoform of protein kinase C (in pyramidal cells) and parvalbumin (in interneurons) was determined in the hippocampal CA1 by applying monoclonal antibodies. Because chronic treatment with the calcium antagonist nimodipine prevents the development of strokes in SHR-SP, we compared SHR-SP (stroke) with age-matched nimodipine-treated rats (nonstroke). RESULTS: After stroke in control animals, we observed a strikingly enhanced immunoreactivity for protein kinase C-gamma in CA1 pyramidal cells compared with nimodipine-treated rats, which can be interpreted as the result of an increased activation of these cells. The pathological increase of protein kinase C-gamma immunoreactivity was accompanied by a reduced parvalbuminergic innervation of these pyramidal cells in symptomatic SHR-SP. CONCLUSIONS: Because parvalbumin is present in a subset of GABAergic inhibitory interneurons, these data suggest that increased activity of CA1 pyramidal cells after spontaneous stroke may partially be related to a decreased inhibitory input on these cells.

Aging↗

PubMed1993

Protective efficacy of a hypothermic pharmacological agent in gerbil forebrain ischemia.

BACKGROUND AND PURPOSE: The novel muscarinic cholinergic partial agonist U-80816E was tested in the gerbil brief bilateral carotid occlusion ischemia model based on the rationale that the compound's hypothermic properties might afford effective protection of the selectively vulnerable hippocampal CA1 region. METHODS: Male gerbils were subjected to either 10 or 15 minutes of bilateral carotid occlusion, followed by histopathological assessment of the CA1 neuronal survival 7 days later. RESULTS: In saline-treated animals, 10 minutes of bilateral carotid occlusion resulted in a 30.5% loss of CA1 neurons, whereas a 15-minute insult resulted in a 49.6% loss. Administration of U-80816E (6 mg/kg i.p. 30 minutes before bilateral carotid occlusion and again 2 hours after reperfusion) resulted in a significant protective effect of the CA1 neuronal population with either duration of ischemia; neuronal loss was reduced to 12.6% in the milder model (p < 0.05 versus saline-treated) and 24.9% in the more severe model (p < 0.04 versus saline). However, the 6 mg/kg i.p. dose of U-80816E was found to produce a 1.0 degree C decrease in brain temperature (measured with a tympanic temperature probe) at 10 minutes of ischemia compared with that of saline-treated gerbils. At 10 minutes of reperfusion, after the 10-minute episode of ischemia, the brain temperature of the U-80816E-treated gerbils was 2.2 degrees C lower than that of saline-treated animals. When the U-80816E-treated gerbils were subjected to either 10 or 15 minutes of ischemia but placed in a heated chamber that prevented the hypothermic effects, no cerebroprotection was observed. CONCLUSIONS: These results show that the anti-ischemic efficacy of U-80816E is mediated through its hypothermic properties, thus suggesting the feasibility of pharmacologically induced hypothermia as a cerebroprotective approach.

Animals↗

PubMed1993

Suppression of protein synthesis in the reperfused brain.

BACKGROUND: Brain ischemia and reperfusion produce profound protein synthesis alterations, the extent and persistence of which are dependent on the nature of the ischemia, the brain region, the cell layer within a region, and the particular proteins studied. After transient ischemia, most brain regions recover their protein synthesis capability; however, recovery in the selectively vulnerable areas is poor. It is unknown whether this phenomenon itself provokes or is a consequence of the process of neuronal death. SUMMARY OF REVIEW: Protein synthesis suppression during ischemia is due to energy depletion, but this is quickly reversed upon recirculation. Reperfusion does not appear to damage DNA or transcription mechanisms, although there are changes in the profile of transcripts being made. Similarly, purified ribosomes isolated from reperfused brains can make the normal repertoire of proteins and heat-shock proteins. However, during early reperfusion, newly synthesized messenger RNAs appear to accumulate in the nucleus; this alteration in RNA handling could reflect disruption at any of several steps, including posttranscriptional processing, nuclear pore transport, cytoskeletal binding, or formation of the translation initiation complex. Another mechanism that may be responsible for protein synthesis suppression during late reperfusion is progressive membrane destruction, with consequent shifts in the concentration of ions crucial for ribosomal function. CONCLUSIONS: Protein synthesis suppression after ischemia likely involves a progression of multiple mechanisms during reperfusion. Although the recent work reviewed here offers new insight into the potential mechanisms disrupting protein synthesis, detailed understanding will require further investigation.

Animals↗

PubMed1995

Nitric oxide synthase inhibition and extracellular glutamate concentration after cerebral ischemia/reperfusion.

BACKGROUND AND PURPOSE: Transient cerebral ischemia in rats results in selective loss of neuronal viability, eg, hippocampal CA1 neurons. The neurochemical variables responsible for this selective vulnerability to ischemia/reperfusion (IR) appear to involve excitatory amino acids. In brain IR, excitatory amino acid toxicity may be modulated by endogenous nitric oxide (NO.) gas. To investigate NO. in global brain IR, we measured the effects of NO. synthase (NOS) inhibition on interstitial excitatory amino acids in rats. Changes in postischemic cerebral blood flow and blood-brain barrier function also were evaluated. METHODS: Forebrain ischemia was produced by systemic hypotension and occlusion of both carotid arteries for 15 minutes. Blood flow was restored for 60 minutes by unclamping the carotids and reinfusing with blood. A microdialysis probe was placed into the cortex and hippocampus using a stereotaxic device. Interstitial glutamate concentration was measured during IR with high-performance liquid chromatography. A competitive NOS inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), was given intraperitoneally 30 minutes before ischemia in doses of 1, 4, and 20 mg/kg. Changes in cerebral blood flow and blood-brain barrier during IR were determined using laser-Doppler flowmetry and microdialysis with sodium fluorescein. RESULTS: Glutamate in the dialysate during IR increased transiently 10-fold and returned to baseline levels by 30 minutes of reperfusion. Animals treated with L-NAME 30 minutes before ischemia also showed increases in glutamate concentration during ischemia, but glutamate remained elevated during reperfusion. The increase in glutamate concentration during reperfusion caused by L-NAME was prevented by L-arginine. The administration of L-arginine and L-NAME together decreased extracellular glutamate concentration during ischemia. Cerebral blood flow decreased to about 5% of baseline values during ischemia but increased approximately fourfold relative to control values on reperfusion. The hyperemic responses after ischemia were not different between IR groups treated with or without L-NAME. Brain ischemia increased the permeability of the blood-brain barrier to fluorescein; however, this change was attenuated by L-NAME administration at 20 mg/kg. CONCLUSIONS: NOS inhibition did not attenuate extracellular glutamate accumulation during ischemia and increased its concentration on reperfusion. The elevated glutamate concentration after IR in L-NAME-treated rats did not appear to be due to either a decrease in cerebral blood flow response after ischemia or increases in local blood-brain barrier permeability. For the most part, the blood-brain barrier was spared in the immediate postischemic period by L-NAME treatment. These data suggest that NO. production may oppose synaptic excitatory amino acid accumulation and presumably excitotoxicity during IR.

Amino Acid Oxidoreductases↗

PubMed1999

Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency.

BACKGROUND AND PURPOSE: We have demonstrated that copper-zinc superoxide dismutase (CuZn-SOD), a cytosolic isoenzyme of SODs, has a protective role in the pathogenesis of superoxide radical-mediated brain injury. Using mice bearing a disruption of the CuZn-SOD gene (Sod1), the present study was designed to clarify the role of superoxide anion in the pathogenesis of selective vulnerability after transient global ischemia. METHODS: Sod1 knockout homozygous mutant mice (Sod1 -/-) with a complete absence of endogenous CuZn-SOD activity, heterozygous mutant mice (Sod1 +/-) with a 50% decrease in the activity, and littermate wild-type mice (male, 35 to 45 g) were subjected to global ischemia. Since the plasticity of the posterior communicating artery (PcomA) has been reported to influence the outcome of hippocampal injury, we assessed the relation between the plasticity of PcomAs and the decrease of regional cerebral blood flow in global ischemia. RESULTS: The fluorescence intensity of hydroethidine oxidation, a measurement of ethidium fluorescence for superoxide radicals, was increased in mutant mice 1 day after both 5 and 10 minutes of global ischemia, compared with wild-type mice. Hippocampal injury in the PcomA hypoplastic brains showed significant exacerbation in mutant mice compared with wild-type littermates 3 days after 5 minutes of global ischemia, although a marked difference was not observed at 1 day. CONCLUSIONS: These data suggest that superoxide radicals play an important role in the pathogenesis of delayed injury in the vulnerable hippocampal CA1 subregion after transient global ischemia.

Animals↗

PubMed2000

Vasodilatory response of border zones to acetazolamide before and after endarterectomy : an echo planar imaging-dynamic susceptibility contrast-enhanced MRI study in patients with high-grade unilateral internal carotid artery stenosis.

BACKGROUND AND PURPOSE: The importance of hemodynamic changes related to a high-grade internal carotid artery (ICA) stenosis remains a matter of controversy. Areas between the vascular territories of major cerebral arteries, namely, the border zones, may be selectively vulnerable to hemodynamic alteration. The aim of this study was to search for any hemodynamic impact of carotid endarterectomy (CEA) on vasodilatory response, in particular, within the border zones, by means of multislice dynamic susceptibility contrast MRI. METHODS: Thirteen patients with a high-grade unilateral ICA stenosis (>80%) were examined. Relative regional cerebral blood volume (rrCBV) was determined separately for white matter, gray matter, and anterior and posterior border zones by the acetazolamide test. A vasomotor reactivity index was evaluated from the rrCBV values. Values from the ipsilateral hemisphere were compared with contralateral ones, before and after CEA. RESULTS: Before CEA, rrCBV values in the anterior border zones were significantly (P<0.05) higher in the ipsilateral hemisphere than in the contralateral hemisphere. A decrease in vasomotor reactivity indexes was also observed in the lesion side, but the difference from the contralateral side was not statistically significant. In posterior border zones, no differences in rrCBV or vasomotor reactivity were found between the ipsilateral and the contralateral hemispheres. After CEA, the rrCBV asymmetry in the anterior border zones cleared. CONCLUSIONS: High-grade ICA stenosis with efficient primary collateral pathways may have an early limited hemodynamic impact within border-zone areas. The favorable course of these abnormalities after surgery suggests an additional benefit of CEA at this stage.

Acetazolamide↗

PubMedDate not supplied

Heterogeneities of regional cerebral blood flow during hypoxia-ischemia in the rat.

The distribution of regional cerebral blood flow (rCBF) within the cerebral hemispheres of rats was investigated following an hypoxic-ischemic insult consisting of a 30-minute exposure to 6.5% to 7% inspired oxygen coupled with unilateral ligation of the common carotid artery and maintenance of normal blood pressure (modified Levine preparation). rCBF was estimated by means of an autoradiographic method employing 14C-antipyrine. Mean arterial PO2 values of 26.8 to 27.5 mm Hg were attained during the insult period. rCBF rose above control values in all structures of the hemisphere contralateral to carotid artery ligation. Structures of the hemisphere ipsilateral to arterial ligation exhibited rCBF values less than those of the opposite side. However, the degree to which carotid artery occlusion reduced the rCBF of a structure relative to that of the opposite hemisphere varied greatly from region to region, with the greatest decrements occurring in the lateral cerebral cortex and the caudoputamen. Previous studies in this model have shown that these regions of the hemisphere ipsilateral to carotid artery occlusion are zones of frequent histological injury. These data suggest that inhomogeneities of rCBF may in part determine the phenomenon of "selective vulnerability" of the nervous system to hypoxia-ischemia.

Animals↗

PubMed2003

Respiratory effects of gestational intermittent hypoxia in the developing rat.

Intermittent hypoxia (IH), one of the hallmarks of obstructive sleep apnea, occurs more frequently during pregnancy. We hypothesized that IH may lead to persistent postnatal changes in respiratory responses to acute hypoxia and may also lead to adverse effects on spatial function learning as revealed by the Morris water maze. To examine this issue, time-pregnant Sprague-Dawley rats were exposed to IH and room air (IHRA; 21 and 10% O2 alternations every 90 seconds) or to normoxia (RARA) until delivery. Ventilatory and metabolic responses to a 20-minute acute hypoxic challenge (10% O2) were conducted at postnatal ages 5, 10, 15, and 30 days. In addition, spatial task learning was assessed in the water maze at 1 and 4 months of age. Normoxic ventilation was higher at all time points in IHRA rats than in RARA rats (p < 0.01). Peak hypoxic ventilatory responses were attenuated in IHRA rats at 5 days of age and hypoxic ventilatory depression was accentuated at this age as well. However, ventilatory equivalents (minute ventilation/oxygen consumption) revealed significant reductions in peak hypoxic ventilatory responses of IHRA rats and hypoxic ventilatory depression at all postnatal ages (p < 0.01). Acquisition and retention of a spatial task were similar in the IHRA and RARA groups at both 1 and 4 months of age. We conclude that gestational intermittent hypoxia elicits long-lasting alterations in the control of breathing. We postulate that such IH-induced respiratory plasticity may create selective vulnerability to hypoxia during development.

Animals↗

PubMed1971

Distribution and fate of 54Mn in the monkey: studies of differnnt parts of the central nervous system and other organs.

The fate and distribution of isotopic manganese administered as a single carrier-free dose of 200 muCi of maleate-(54)Mn to 12 rhesus monkeys was studied at different time periods from the 6th hr to the 278th day. Whole-body activity was measured, and all body organs and tissues and different parts of the central nervous system (CNS) were evaluated for specific activity, exponential analysis, and relative retention. Exponential analysis revealed a pattern of discharge with a fast and a slow component for the whole body and for many of the viscera. All parts of the CNS and, to a lesser degree, the thyroid and muscle showed an almost steady state of activity after the initial uptake. While the whole body and most organs and tissues appeared to discharge their radioactivity with the passage of time, first rapidly and then gradually, the CNS, endocrine glands, and muscle tissues showed persistent levels of specific activity. All components of the brain exhibited increasing relative retention, the lentiform nucleus and the cerebellum showing this more. It is suggested that the selective vulnerability of the brain in manganese miners might result from this inability on the part of the CNS to discharge the (54)Mn with time. This investigation confirms and amplifies our earlier similar study on the rat.

Animals↗

PubMed2006

Microtubule: a common target for parkin and Parkinson's disease toxins.

Parkinson's disease (PD) is characterized by the selective loss of nigral dopaminergic (DA) neurons, which have long axons enriched with microtubules. Depolymerization of microtubules by PD toxins such as rotenone disrupts vesicular transport. The ensuing accumulation of vesicles in the cell body leads to increased cytosolic concentration of dopamine due to leakage of the vesicles. Elevated oxidative stress induced by dopamine oxidation may thus trigger the selective demise of DA neurons. Many strategies have been developed to protect DA neurons by stabilizing microtubules either directly or through intracellular signaling cascades. On the other hand, parkin, one of the most frequently mutated genes in PD, encodes for a protein-ubiquitin E3 ligase that strongly binds to microtubules. Parkin stabilizes microtubules through three domains that provide strong and independent interactions with tubulin and microtubules. These interactions anchor parkin on microtubules and may facilitate its E3 ligase activity on misfolded proteins transported along microtubules. Thus, parkin and rotenone, two prominent genetic and environmental factors linked to PD, act in an opposing manner on the same molecular target in the cell, microtubules, whose destruction underlies the selective vulnerability of dopaminergic neurons.

Animals↗

PubMed2000

Behavioral effects of transient cerebral ischemia.

CA1 neurons in the hippocampus, a brain structure involved in learning and memory, are selectively vulnerable to ischemic effects. In this study, the authors examined if duration of ischemia is directly related to extent of CA1 damage and degree of spatial learning deficit. Adult female Wistar rats received either 5-min or 10-min ischemia or sham surgery. Following recovery, rats were tested in the Morris water maze. Histological analysis showed moderate cell loss in CA1 (31%) and CA3 (12%) and minimal cell loss in CA2 (4%) with 5-min ischemia. Increased cell loss was seen in CA1 (68%), CA2 (16%), and CA3 (23%) with 10-min ischemia. Behavioral testing revealed that animals with 10-min ischemia have greater spatial learning deficits and they remain impaired across the test days compared to the 5-min ischemic group. Furthermore, degree of CA1 cell loss accounted for approximately 45% of the variance in spatial learning deficits in the ischemic group. The authors conclude that cell loss is largely confined to CA1 region in rats who received 5 and 10 min of ischemia and that increased ischemic duration results in persistent learning deficits in female rats; also, the degree of behavioral impairment is related to extent of CA1 cell loss.

Animals↗

PubMed1997

Screening for Leber's hereditary optic neuropathy associated mitochondrial DNA mutations in patients with prominent optic neuritis.

Previous case reports demonstrated the presence of Leber's hereditary optic neuropathy (LHON) associated mitochondrial (mt) DNA mutations in patients presenting with prominent optic neuritis (PON). By screening the mtDNA, we have excluded the presence of these mutations in 22 patients with PON, indicating that the frequency of these mutations is less than 4.5% in our selected patient population. Reviewing the clinical data of these patients revealed that severe optic nerve atrophy developed in association with both the benign and the severely disabling form of Multiple Sclerosis (MS). This observation suggests that the prominent feature of ON in MS may be related to local factors or to a selective vulnerability of the optic nerve in some patients. However, it also may be consequence of a deleterious process associated with inflammatory demyelination in the central nervous system (CNS) of another, genetically probably distinct subgroup of severely disabled patients.

Adult↗

PubMed1989

Acute action of DSP-4 on central norepinephrine axons: biochemical and immunohistochemical evidence for differential effects.

Previous immunohistochemical studies of the long-term effects of the noradrenergic neurotoxin DSP-4 have demonstrated a remarkably selective vulnerability of norepinephrine (NE) axons of the locus coeruleus (LC). NE axons originating in non-LC NE neurons appear to be largely resistant to the neurotoxic action of DSP-4. We conducted this study to evaluate the acute effects of DSP-4 on NE axons in four different brain regions: cerebral cortex, cerebellum, ventral forebrain, and hypothalamus. NE levels were determined by high-performance liquid chromatography (HPLC) 6 and 24 hr and 14 days after DSP-4 administration. NE axons in these brain regions were visualized in brain sections at 6 and 24 hr after drug treatment, using a specific antiserum to NE. HPLC assays revealed profound reductions of NE levels in cerebral cortex and cerebellum, but only minor decreases in ventral forebrain and hypothalamus. NE immunohistochemistry showed dramatic differences in the acute effects of DSP-4 on NE axon staining: nearly complete loss of staining in cortex and cerebellum, in contrast to an almost unchanged staining pattern in ventral forebrain and hypothalamus. This study demonstrates that NE immunohistochemistry is a valuable tool to assess the acute effects of DSP-4 on NE axons in different brain regions. The results provide the first direct evidence that NE axons are not uniformly acted on by DSP-4 and suggest that the acute effects of DSP-4 are restricted to LC axons.

Animals↗

PubMed2005

Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: metabolic inhibitors, MPTP, and methamphetamine.

A number of strategies using the nutritional approach are emerging for the protection of the brain from damage caused by metabolic toxins, age, or disease. Neural dysfunction and metabolic imbalances underlie many diseases, and the inclusion of metabolic modifiers may provide an alternative and early intervention approach that may prevent further damage. Various models have been developed to study the impact of metabolism on brain function. These have also proven useful in expanding our understanding of neurodegeneration processes. For example, the metabolic compromise induced by inhibitors such as 3-nitropropionic acid (3-NPA), rotenone, and 1-methyl-4-phenylpyridinium (MPP+) can cause neurodegeneration in animal models and these models are thought to simulate the processes that may lead to diseases such as Huntington's and Parkinson's diseases. These inhibitors of metabolism are thought to selectively kill neurons by inhibiting various mitochondrial enzymes. However, the eventual cell death is attributed to oxidative stress damage of selectively vulnerable cells, especially highly differentiated neurons. Various studies indicate that the neurotoxicity resulting from these types of metabolic compromise is related to mitochondrial dysfunction and may be ameliorated by metabolic modifiers such as L-carnitine (L-C), creatine, and coenzyme Q10, as well as by antioxidants such as lipoic acid, vitamin E, and resveratrol. Mitochondrial function and cellular metabolism are also affected by the dietary intake of essential polyunsaturated fatty acids (PUFAs), which may regulate membrane composition and influence cellular processes, especially the inflammatory pathways. Cellular metabolic function may also be ameliorated by caloric restriction diets. L-C is a naturally occurring quaternary ammonium compound that is a vital cofactor for the mitochondrial entry and oxidation of fatty acids. Any factors affecting L-C levels may also affect ATP levels. This endogenous compound, L-C, together with its acetyl ester, acetyl-L-carnitine (ALC), also participates in the control of the mitochondrial acyl-CoA/CoA ratio, peroxisomal oxidation of fatty acids, and production of ketone bodies. A deficiency of carnitine is known to have major deleterious effects on the CNS. We have examined L-C and its acetylated derivative, ALC, as potential neuroprotective compounds using various known metabolic inhibitors, as well as against drugs of abuse such as methamphetamine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1982

Aging, senile dementia, and the intralaminar microchemistry of cerebral cortex.

We compared the microchemical architecture or right frontal isocortex from patients with senile dementia and age-matched and younger controls. Neuronal connectivity within deep lamina of the cortical column (Brodmann area 9) tended to decline in normal aging and was profoundly depleted in senile dementia. In both aging and senile dementia, there was a significant 20% loss of total cells (neurons and glia) in cortical layers III to VI. In senile dementia, marked diminution of total ganglioside sialic acid per neuron and galactocerebroside per cell in the lower lamina far exceeded alterations associated with aging itself. This structural loss may imply deafferentation of the cortex, owing to loss of projections from subcortical areas such as nucleus basalis. Selective vulnerability of axodendritic arborization of neurons in lower lamina may be correlated to the impaired cognitive functions of senile dementia.

Adult↗

PubMed1983

Motor neuron disease (ALS): evaluation of detection thresholds of cutaneous sensation.

Cutaneous touch-pressure, vibration, and thermal cooling detection thresholds were estimated on the skin of one foot for 80 patients with motor neuron disease (MND) and compared with that of more than 300 site, age, and sex-matched healthy controls. Fourteen of the patients had elevated thresholds (greater than or equal to 95th percentile): 7 showed elevated thresholds of sensitive points, 5 an increased number of insensitive grid points, and 2 a combination of these criteria. Therefore, raised vibration thresholds occur more frequently in MND patients than in controls (p less than 0.001). A detection threshold abnormality was not demonstrated for touch-pressure or for thermal cooling. These results are in keeping with the demonstrated increased cutaneous myelinated fiber degeneration in this condition and with evidence of sensory neural system involvement at postmortem examination. Although motor neurons are selectively vulnerable in MND, afferent neurons may also be affected, albeit less frequently and/or to a lesser degree.

Adult↗

PubMed1986

Hyperglycemia does not augment neuronal damage in experimental status epilepticus.

The neuronal regions affected and the neuropathologic features of ischemia and status epilepticus are similar. Experimentally, elevated plasma glucose levels, increasing brain lactate, are associated with more severe neuropathologic damage from cerebral ischemia. We therefore studied the cytologic features and cerebral content of lactate and glucose in the selectively vulnerable neurons of rat hippocampus after 2 hours of L-allylglycine-induced status epilepticus in rats with mean plasma glucose concentrations of 65, 250, and 480 mg/100 ml. Brain lactate concentration was elevated in status and maximal in the high-glucose group, but the maximum levels (8 mumol/g) were less than those thought to augment cell death in ischemia. Using multiple linear regressions, only time-in-status predicted neuropathologic damage.

Animals↗