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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.
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PMID:Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response. 1104 75

This article addresses syndromes that clinically and/or radiologically resemble acute stroke. These syndromes generally fall into four categories. (1) Patients with acute neurological deficits with nonischemic lesions and no acute abnormality on diffusion-weighted images. These patients may have peripheral vertigo, migraines, seizures, dementia, functional disorders, amyloid angiopathy, or metabolic disorders. When these patients present, we can confidently predict that they are not undergoing infarction. (2) Patients with ischemic lesions with reversible clinical deficits. Nearly 50% of patients with transient ischemic attacks have lesions with restricted diffusion. Patients with transient global amnesia may have punctate lesions with restricted diffusion in the medial hippocampus, parahippocampal gyms, and corpus callosum. (3) Vasogenic edema syndromes that may mimic acute infarction clinically and on conventional imaging. These include eclampsia/hypertensive encephalopathy, other posterior leukoencephalopathies, human immunodeficiency virus encephalopathy, hyperperfusion syndrome following carotid endarterectomy, venous sinus thrombosis, acute demyelination, and neoplasm. These syndromes demonstrate elevated diffusion rather than the restricted diffusion associated with acute ischemic stroke. (4) Entities in which restricted diffusion may resemble acute infarction. These include pyogenic infections, herpes virus encephalitis, Creutzfeldt-Jakob disease, diffuse axonal injury, tumors with dense cell packing, and rare acute demyelinative lesions.
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PMID:Diffusion-weighted imaging as a problem-solving tool in the evaluation of patients with acute strokelike syndromes. 1114 28

Neurological diseases are frequently associated with axonal degeneration, which leads to dysfunction though separation of neurons from their targets. The mechanisms of axonal degeneration are largely unknown and in many cases are independent of those occurring within cell bodies in neurodegenerative disorders. The Wld(s) mouse mutant demonstrates the unique phenotype of resistance to axonal degeneration after axotomy (slow Wallerian degeneration), making it a powerful tool for studying mechanisms of axonal degeneration. We asked whether the Wld(s) mutation also provides resistance to axonal degeneration in a slowly progressing neuropathy. Using cultured dorsal root ganglion neurons we compared the course of axonal degeneration in response to exposure to the neurotoxin vincristine and found that Wld(s) neurites were relatively resistant to vincristine neuropathy. These findings suggest common pathophysiologic mechanisms between axotomy-induced Wallerian degeneration and toxic neuropathy. The implications are wide-ranging and are relevant to the pathophysiology of axonal degeneration seen in a wide spectrum of neurological diseases ranging from stroke and head trauma to spinal cord injury and peripheral neuropathy.
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PMID:The gene for slow Wallerian degeneration (Wld(s)) is also protective against vincristine neuropathy. 1116 49

Diffusion imaging is a noninvasive technique for measuring the movement of water molecules. Although it has had its greatest impact thus far in the area of stroke imaging, the information garnered from diffusion experiments can provide an indication of myelin injury and perhaps axonal integrity. In this paper, we describe some current and potential future applications of diffusion imaging in multiple sclerosis. These include the use of global indices such as diffusion trace and anisotropy, as well as implementation of axonal fiber tracking methodologies for assessment of axonal integrity and connectivity between cortical regions.
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PMID:Future applications of DWI in MS. 1133 91

Estrogen and progesterone, long considered for their roles as primary hormones in reproductive and maternal behavior, are now being studied as neuroprotective and neuroregenerative agents in stroke and traumatic brain injuries. Collectively, the hormones reduce the consequences of the injury cascade by enhancing anti-oxidant mechanisms, reducing excitotoxicity (altering glutamate receptor activity, reducing immune inflammation, providing neurotrophic support, stimulating axonal remyelinization), and enhancing synaptogenesis and dendritic arborization. Estrogen seems more effective as a prophylactic treatment in females at risk for cardiac and ischemic brain injury, whereas progesterone appears to be more helpful in the post-injury treatment of both male and female subjects with acute traumatic brain damage. However, a recent clinical trial with estradiol replacement therapy in elderly women that have a history of cerebrovascular disease, showed that this hormone was unable to protect against reoccurrence of ischemia or to reduce the incidence of mortality compared to a placebo.
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PMID:Brain damage, sex hormones and recovery: a new role for progesterone and estrogen? 1141 Feb 69

Cortical strokes alter functional maps but associated changes in connections have not been documented. The neuroanatomical tracer biotinylated dextran amine (BDA) was injected into cortex bordering infarcts 3 weeks after focal strokes in rat whisker barrel (somatosensory) cortex. The mirror locus in the opposite hemisphere was injected as a control. After 1 week of survival, brains were processed for cytochrome oxidase (CO)-, Nissl-, and BDA-labeled neurons. Cortex bordering the infarct (peri-infarct cortex) had abnormal CO and Nissl structure. BDA-labeled neurons were plotted and projections were analyzed quantitatively. Animals with small strokes had intracortical projections, arising from peri-infarct cortex, not seen in normal hemispheres: the overall orientation was statistically significantly different from and rotated 157 degrees relative to the controls. Compared to the controls, significantly fewer cells were labeled in the thalamus. Thus, after focal cortical stroke, the peri-infarct cortex is structurally abnormal, loses thalamic connections, and develops new horizontal cortical connections by axonal sprouting.
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PMID:New patterns of intracortical projections after focal cortical stroke. 1159 58

Biochemical markers of brain damage, e.g. ischemic stroke, should reflect the volume of irreversibly damaged brain parenchyma and the clinical outcome in a single patient in order to allow estimation of prognosis at an early stage. Tau protein, which derives predominantly from neurons and axons, is elevated in the cerebrospinal fluid of patients with neurodegenerative disease. This makes tau protein a potential marker of neuronal/axonal injury. In order to test this hypothesis, the current study aimed at showing that tau protein is measurable in the blood after acute ischemic stroke and that it correlates with clinical disability and stroke volume. In a longitudinal prospective study we measured tau protein serum levels with an ELISA in 30 patients longitudinally after ischemic stroke. Tau protein was detectable within 5 days after ischemia in the sera of 7/20 patients with MRI-proven infarction and in 2/10 patients with transitory ischemic attack; both of them had a small infarction visible on the MRI scan. Tau protein was measurable within 6 h after symptom onset, peaked after 3-5 days and correlated with infarct volume and disability after 3 months. In conclusion, serum tau protein is a candidate marker of axonal injury. In stroke, its clinical use is limited, because it is detectable only in a proportion of patients.
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PMID:Serum tau protein level as a marker of axonal damage in acute ischemic stroke. 1180 92

In addition to the systemic renin-angiotensin system (RAS), a local RAS has been identified. Recent research has focused on this latter system and has investigated the effects of locally generated angiotensin II, especially in the kidney, heart and CNS. In the mammalian brain, all components of the RAS are present including angiotensin AT(1) and AT(2) receptor subtypes. While the AT(1) receptor is responsible for the classical effects of angiotensin II, it has been found that the AT(2) receptor displays totally different signalling mechanisms and this has revealed hitherto unknown functions of angiotensin II. AT(2) receptors are expressed at low density in many healthy adult tissues, but are up-regulated in pathological circumstances, e.g. stroke or nerve lesion. Evidence has now emerged that the actions of angiotensin II that are exerted via the AT(2) receptor are directly opposed to those mediated by the AT(1 )receptor. For example, the AT(2) receptor has antiproliferative properties and therefore opposes the growth-promoting effect linked to AT(1) receptor stimulation. It has been reported that the AT(2) receptor regulates several functions of nerve cells, e.g. ionic fluxes, cell differentiation and axonal regeneration, but also modulates programmed cell death. It is possible that a more extensive knowledge of the AT(2) receptor could contribute to the understanding of the clinically beneficial effects of AT(1) receptor antagonists, as this treatment may unmask AT(2) receptor activity. This review presents selected aspects of advances in AT(2) receptor pharmacology, molecular biology and signal transduction with particular reference to possible novel therapeutic options for CNS diseases.
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PMID:Angiotensin AT2 receptor ligands: do they have potential as future treatments for neurological disease? 1188 35

Neuropilin-1 and -2 (NP-1/NP-2) are transmembrane receptors that play a role in axonal guidance by binding of class III semaphorins, and in angiogenesis by binding of the vascular endothelial growth factor isoform VEGF165 and placenta growth factor (PLGF). We investigated the expression pattern of NP-1/NP-2, their co-receptors, vascular endothelial growth factor receptor-1 and -2 (VEGFR-1, VEGFR-2), and their ligands, class III semaphorins, VEGF and PLGF, following experimental cerebral ischemia in mice. By means of in situ hybridization and immunohistochemistry we observed loss of expression of class III semaphorins in neurons in the infarct/peri-infarct area. In contrast, we observed high expression of NP-1 in vessels, neurons, and astrocytes surrounding the infarct. VEGF and PLGF were upregulated in different cell types following stroke. Our results suggest a shift in the balance between semaphorins and VEGF/PLGF, which compete for NP-binding. Possibly, the loss of semaphorins facilitates binding of the competing ligands (VEGF/PLGF), thus inducing angiogenesis. In addition, the observed expression patterns further suggest a neurotrophic/neuroprotective role of VEGF/PLGF.
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PMID:Cell type-specific expression of neuropilins in an MCA-occlusion model in mice suggests a potential role in post-ischemic brain remodeling. 1193 89

Vascular endothelial growth factor (VEGF) was originally discovered as an endothelial-specific growth factor. While the predominant role of this growth factor in the formation of new blood vessels (angiogenesis) is unquestioned, recent observations indicate that VEGF also has direct effects on neurons and glial cells, and stimulates their growth, survival and axonal outgrowth. Because of these pleiotropic effects, VEGF has now been implicated in several neurological disorders both in the preterm infant (leukomalacia) and the adult (stroke, neurodegeneration, cerebral and spinal trauma, ischemic and diabetic neuropathy, nerve regeneration). A challenge for the future is to unravel to what extent the effect of VEGF in these disorders relates to its angiogenic activity or direct neurotrophic effect.
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PMID:Vascular and neuronal effects of VEGF in the nervous system: implications for neurological disorders. 1196 70


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