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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Besides distal symmetrical sensory polyneuropathy (DSSP), middle-aged diabetic patients may present with focal or multifocal neuropathies, including proximal neuropathy of the lower limbs, the pathophysiological features of which are uncertain. We studied 10 non-insulin-dependent diabetic patients, 45 to 72 years of age, who developed a painful proximal neuropathy of the lower limbs for which other causes of neuropathy were carefully excluded. The proximal neuropathy was asymmetrical in all patients, sensory in 4, motor and sensory in the others. Signs of DSSP were present in all. A sample of the intermediate cutaneous nerve of the thigh, a sensory branch of the femoral nerve, was taken by biopsy and examined by light and electron microscopy. Examination of the nerve specimens revealed ischemic nerve lesions in 3 patients. Nerve ischemia was associated with vasculitis and inflammatory infiltration in 2 of them. In the other patients the lesions of the cutaneous nerve of the thigh included a varying incidence of axonal and demyelinative lesions similar to those observed in DSSP, with mild inflammatory infiltration in 4 of them. The density of myelinated and of unmyelinated was variably decreased. This study shows that axonal and demyelinative lesions similar to those found in diabetic DSSP are present in proximal nerves in mild forms of proximal diabetic neuropathy; while nerve ischemia, inflammatory infiltration, and vasculitis are encountered in the most severe forms of proximal diabetic neuropathy.
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PMID:Nerve biopsy findings in different patterns of proximal diabetic neuropathy. 817 2

The characterization of sensory, motor and cognitive dysfunctions following occlusion of the middle cerebral artery (MCA) is prerequisite to investigations of treatment intervention in animal models of ischemia. Different strategies are used to induce ischemia, but the focal, transient occlusion of the MCA has been reported to result in neuropathology most similar to that seen in clinical cerebral ischemia. If the MCA occlusion technique results in a stroke animal model, then the behavioral impairments inherent in stroke should be manifested in this model. The present study provides a further characterization of behavioral alterations associated with MCA occlusion. Sprague-Dawley rats underwent temporal occlusion of the right MCA, and at 1 mo and 2 mo postischemia, were subsequently tested in passive avoidance behavior, motor coordination, asymmetrical motor behavior, neurological functioning, nocturnal spontaneous and amphetamine-induced locomotor activity, and haloperidol-induced catalepsy. Results revealed that ischemic rats showed long-term impairments in sensory, motor and cognitive functions. The discrepancy with other studies reporting temporal MCA-induced behavioral deficits may be due to techniques used to induce ischemia and consequent CNS damage, differences in time period of testing (i.e., immediate vs. later postischemia, nighttime vs. daytime), number of test-retests over the course of the experiment, and age of the animals. The mechanism involved in the MCA-induced behavioral changes may be represented by loss of dopamine receptors on striatal neurons. Histological analysis revealed damage limited to the lateral aspect of the striatum. These behavioral and anatomical data support MCA occlusion as a model of ischemia, and elucidate important factors that should be controlled for in characterizing the MCA-induced neuropathological alterations.
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PMID:Locomotor and passive avoidance deficits following occlusion of the middle cerebral artery. 857 87

Alterations in left ventricle (LV) wall motion induced by ischemia will affect flow dynamics, and these altered flow fields can be used to evaluate LV pumping efficiency. LV chamber flow fields were obtained in this study by solving the discretized three-dimensional Navier-Stokes equations for viscous, incompressible unsteady flow by using the finite analytic method. Several cases of abnormal wall motion (AWM) were simulated by a manipulation of the boundary conditions to produce regions of hypokinesis, akinesis, and dyskinesis. These solutions were used to determine the central ejection region (CER), defined as the region of flow domain in which the obtained velocity field vectors are aligned +/- 3 degrees from the LV long axis. A CER coefficient was computed from information on the location and orientation of the CER within the LV cavity. Contraction of the spherical ventricle produced a vector field that was symmetric with respect to the long axis. For the simulations of AWM, an asymmetrical flow pattern developed, became more pronounced with increasing severity of AWM, and resulted in a shorter CER that shifted toward the ischemic region. The CER coefficients decreased monotonically with increased severity in AWM from 0.948 in the normal case to a low of 0.164 for the most severe case of AWM. The CER coefficient quantitatively displayed the sensitivity of the flow patterns to even moderate degrees of hypokinesis. In addition, visualization of the three-dimensional flow field reinforced the necessity of three-dimensional simulations to capture aspects of the flow that existing methods of two-dimensional flow imaging that use ultrasound may miss.
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PMID:A simulation of three-dimensional systolic flow dynamics in a spherical ventricle: effects of abnormal wall motion. 866 17

In rats, acute injury of neurons in the caudate nucleus (CN) and globus pallidus (GP) by local injection of ibotenic acid (IA) or by transient forebrain ischemia has caused transneuronal cell death of neurons in the substantia nigra reticulata (SNr) weeks after the initial injury. Recently transient expression of an immediate early gene c-fos was induced specifically in neurons of the subthalamic nucleus (STN) and SNr at 36-48 h after the IA-lesions, prior to the delayed degeneration of SNr neurons. These cellular and molecular events may alter the level of inhibitory output from the basal ganglia and lead to movement disorders. To test (i) whether movement disorders occur in the early period after unilateral lesions of the CN and GP by IA-injection, and (ii) whether ablation of the STN reverses the early movement disorders, we used a modified version of Porsolt forced swim test in which the lesion-induced asymmetry of motor function becomes apparent as rotation when the animals are forced to swim. Following unilateral IA-lesions of the right CN and GP in rats, rapid contraversive rotation appeared transiently 36-48 h after the lesions, and, in turn, slow ipsiversive rotation appeared at 3-5 days postlesion. Prior ablation of the ipsilateral STN reversed these early movement disorders produced by the unilateral IA-lesions of the CN and GP and instead created persistent contraversive rotation 7-10 days after the lesions. Each phase of the dominant rotation behavior was dependent on asymmetrical limb motor activity; decreased left limb activity caused contraversive rotation, and increased left limb activity caused ipsiversive rotation. Reversal of these early movement disorders suggests that ablation of the STN prevents the transneuronal degeneration of the SNr.
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PMID:Behavioral correlates of transneuronal degeneration of substantia nigra reticulata neurons are reversed by ablation of the subthalamic nucleus. 907 73

Neurons in the dorsal neostriatum are highly vulnerable to transient cerebral ischemia. It has been suggested that excessive dopamine release during ischemia may play an important role in the pathogenesis of postischemic cell death in the neostriatum. However, it remains controversial whether depletion of dopamine protects neurons in the neostriatum against ischemic insult. In the present study, transient forebrain ischemia was induced using the four-vessel occlusion method. Ischemic depolarization was used as an indication of completed ischemia. Under our experimental conditions, ischemia that produces approximately 21 min ischemic depolarization caused more than 90% of cell death in the dorsolateral neostriatum. Using such ischemia as a standard insult, the effect of dopamine depletion on neostriatal neurons after ischemia was investigated. Dopamine depletion was produced by unilateral injection of 6-OHDA into the substantia nigra. No difference was found between the number of surviving neurons in the left and the right neostriatum after depletion of dopamine on the left side. In contrast, surviving neurons dramatically increased in the right neostriatum after depletion of dopamine on the right side. These results clearly demonstrate an asymmetrical protection of neostriatal neurons against ischemia after dopamine depletion. The mechanisms of this asymmetrical protection may clarify dopamine action on neuronal injury following cerebral ischemia.
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PMID:Asymmetrical protection of neostriatal neurons against transient forebrain ischemia by unilateral dopamine depletion. 922 58

Vasculitis involving peripheral nerves usually presents as an acute asymmetrical axonal neuropathy. We report a 67-year-old man with a symmetrical subacute neuropathy in which nerve conduction studies showed prominent conduction block, a finding indicative of demyelination. Sural nerve biopsy showed a vasculitic neuropathy with invasion of blood vessel walls by inflammatory cells and a mixture of nerve fiber loss and demyelination. The demyelination in this case was presumably a consequence of subinfarctive nerve ischemia.
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PMID:Conduction block in vasculitic neuropathy. 1039 22

Spiny neurons in the neostriatum are highly vulnerable to cerebral ischemia. Recent studies have shown that the postischemic cell death in the right striatum was reduced after ipsilateral dopamine denervation whereas no protection was observed in the left striatum after dopamine denervation in the left side. In order to reveal the mechanisms of such asymmetrical protection, electrophysiological changes of dopamine-denervated striatal neurons were compared after ischemia between the left and right striatum using intracellular recording and staining techniques in vivo. No difference in cortically evoked initial excitatory postsynaptic potentials was found between the left and right striatum in intact animals after ipsilateral dopamine denervation. The initial excitatory postsynaptic potentials in the dopamine-denervated right striatum were suppressed after transient forebrain ischemia while no significant changes were found in the dopamine-denervated left striatum. Paired-pulse tests suggested that these changes involved presynaptic mechanisms. Although the incidence of a late depolarizing postsynaptic potential elicited by cortical stimulation increased after ischemia in both sides, the increase was greater in the left side. The analysis of current-voltage relationship of spiny neurons indicated that inward rectification in the left striatum transiently disappeared shortly after ischemia whereas that in the right side remained unchanged. The intrinsic excitability of spiny neurons in both sides were suppressed after ischemia, however, the suppression in the right side was stronger than in the left side. The above results demonstrate that after ipsilateral dopamine denervation, the depression of excitatory synaptic transmission and neuronal excitability in the right striatum is more severe than that in the left striatum following ischemia. The depression of excitatory synaptic transmission and neuronal excitability, therefore, might play an important role in neural protection after ischemic insult.
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PMID:Asymmetrical changes of excitatory synaptic transmission in dopamine-denervated striatum after transient forebrain ischemia. 1220 1

The left and right neocortex of the brain has been shown to exert asymmetrical effects on the immune system. In the present study, we used a middle cerebral artery (MCA) occlusion model in Wistar rats to analyze the influence of unilateral CNS ischemia on spleen cell number and function. The occlusion time was 1 h, followed by reperfusion with survival for 0, 2, 7, 14, and 28 days. Changes in plasma norepinephrine levels were used as an index of peripheral sympathetic activity. Results showed that the total number of spleen cells significantly decreased after 2-28 days of survival in animals with cerebral ischemia compared to sham-operated controls. There was no change in the percentage of CD5(+)-CD4(+) T cells, MHC class II(+) cells, or ED1(+) macrophages. However, the percentage of CD5(+)-CD8(+) T cells decreased at 2 days, resulting in an increased CD4/CD8 ratio, and both parameters returned to control levels after 7 days. Mitogen-induced T and B lymphocyte proliferation increased after 0-28 days post-ischemia independently of the mitogen used. There was no difference in immune response or norepinephrine levels between left and right MCA occlusions. These results are consistent with the notion that cerebral ischemia induces mobilization of certain immune cells from the periphery to the brain, where they may contribute to the local inflammatory response. Additionally, the data indicate that cerebral ischemia is followed by a systemic activation of T and B lymphocytes. Absence of asymmetric effects of left versus right stroke, and failure to demonstrate any suppressive effects of left-sided lesions on lymphocyte proliferation, probably reflects the fact that these large cerebral ischemic lesions affect both cortical and subcortical areas.
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PMID:Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats. 1241 24

Melatonin attenuates the short-term consequences of brain ischemia in several animal models. However, there is scant information regarding its efficacy for improving the long-term outcome. To further address that issue, we subjected gerbils to 5-min bilateral carotid occlusion. Some gerbils received acute peri-surgical administration of melatonin while others received continuous melatonin in their water. The gerbils' brains were histologically assessed at 20 wk postsurgery. Chronic but not acute melatonin attenuated ischemia-induced hyperactivity at 3 days postsurgery. Twenty weeks postsurgery, the ischemic gerbils showed varying degrees of bilateral loss of hippocampal CA1 pyramidal cells and elevation of glial fibrillary acidic protein immunoreactivity there. Both the cell loss and the immunoreactivity were markedly asymmetrical for some gerbils. Neither acute nor chronic melatonin altered this pattern of CA1 cell loss and glial immunoreactivity increase. Ischemia increased the number of CA1 cells that were immunoreactive for doublecortin (DCX), a marker for newborn neurons. This increase in CA1 DCX expression was not affected by either melatonin treatment. However, both acute and chronic melatonin reduced the number of DCX immunoreactive neurons in the dentate gyrus. Thus, neither acute nor chronic melatonin altered the long-term neural outcome of forebrain ischemia, although chronic administration seemed to attenuate the short-term behavioral effect. It is suggested that persistently high brain levels of melatonin may be essential for long-term neuroprotection against ischemia. The possibility that melatonin may modulate hippocampal neurogenesis merits further exploration both in normal animals and in models of brain insult.
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PMID:Chronic and acute melatonin effects in gerbil global forebrain ischemia: long-term neural and behavioral outcome. 1828 66

Oxidative stress contributes to cardiovascular complications of diabetes, in part, by reducing the bioavailability of nitric oxide (NO). We investigated the mechanisms whereby the insulin sensitizer rosiglitazone may ameliorate oxidative stress in the vasculature of spontaneously hypertensive rats (SHR). Nine-week-old SHR were treated by gavage for 7 wk with rosiglitazone (5 mg x kg(-1) x day(-1)) or vehicle control. Treatment of SHR with rosiglitazone lowered systolic blood pressure, reduced fasting plasma insulin and asymmetrical dimethylarginine, and increased insulin sensitivity (when compared with vehicle treatment). In vessel homogenates and serum from rosiglitazone-treated SHR, SOD activity was enhanced, while 8-iso-PGF(2alpha) (lipid peroxidation product) was reduced (when compared with samples from vehicle-treated SHR). Moreover, expression of p22phox (catalytic subunit of NADPH oxidase) as well as nitrotyrosine and superoxide content were all reduced in the aortas of rosiglitazone-treated SHR. In mesenteric vascular beds (MVB) isolated ex vivo from rosiglitazone-treated SHR, NO-dependent vasodilator actions of insulin were improved when compared with MVB from vehicle-treated SHR. Acute pretreatment of MVB from vehicle-treated SHR with apocynin (NADPH oxidase inhibitor) enhanced vasodilator actions of insulin (results comparable to those in MVB from rosiglitazone-treated SHR). In Langendorff heart preparations from rosiglitazone-treated SHR, ischemia/reperfusion injury caused infarcts 40% smaller than in hearts from vehicle-treated SHR. Acute pretreatment of hearts from vehicle-treated SHR with apocynin produced similar results. Finally, rosiglitazone treatment of endothelial cells in primary culture reduced superoxide induced by insulin-resistant conditions. We conclude that rosiglitazone therapy in SHR increases SOD activity and decreases p22phox expression in the vasculature to reduce oxidant stress leading to an improved cardiovascular phenotype.
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PMID:Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature. 1953 37


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