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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Temperature is known to influence the extent of anoxic/ischemic injury in gray matter of the brain. We tested the hypothesis that small changes in temperature during anoxic exposure could affect the degree of functional injury seen in white matter, using the isolated rat optic nerve, a typical CNS white matter tract (Foster et al., 1982). Functional recovery after anoxia was monitored by quantitative assessment of the compound action potential (CAP) area. Small changes in ambient temperature, within a range of 32 to 42 degrees C, mildly affected the CAP of the optic nerve under normoxic conditions. Reducing the temperature to < 37 degrees C caused a reversible increase in the CAP area and in the latencies of all three CAP peaks; increasing the temperature to > 37 degrees C had opposite effects. Functional recovery of white matter following 60 min of anoxia was strongly influenced by temperature during the period of anoxia. The average recovery of the CAP, relative to control, after 60 min of anoxia administered at 37 degrees C was 35.4 +/- 7%; when the temperature was lowered by 2.5 degrees C (i.e., to 34.5 degrees C) for the period of anoxic exposure, the extent of functional recovery improved to 64.6 +/- 15% (p < 0.00001). Lowering the temperature to 32 degrees C during anoxic exposure for 60 min resulted in even greater functional recovery (100.5 +/- 14% of the control CAP area). Conversely, if temperature was increased to > 37 degrees C during anoxia, the functional outcome worsened, e.g., CAP recovery at 42 degrees C was 8.5 +/- 7% (p < 0.00001). Hypothermia (i.e., 32 degrees C) for 30 min immediately following anoxia at 37 degrees C did not improve the functional outcome. Many processes within the brain are temperature sensitive, including O2 consumption, and it is not clear which of these is most relevant to the observed effects of temperature on recovery of white matter from anoxic injury. Unlike the situation in gray matter, the temperature dependency of anoxic injury cannot be related to reduced release of excitotoxins like glutamate, because neurotransmitters play no role in the pathophysiology of anoxic damage in white matter (Ransom et al., 1990a). It is more likely that temperature affects the rate of ion transport by the Na(+)-Ca2+ exchanger, the transporter responsible for intracellular Ca2+ loading during anoxia in white matter, and/or the rate of some destructive intracellular enzymatic mechanism(s) activated by pathological increases in intracellular Ca2+.
J Cereb Blood Flow Metab 1992 Nov
PMID:Effects of temperature on evoked electrical activity and anoxic injury in CNS white matter. 140 Jun 52

To study the effects of focal infarction on the capacity for functional activation of an ipsilateral somatosensory system remote from the lesion, we produced a small thrombotic infarct in the left frontal pole of male Wistar rats by a photochemical method. Five days later, the awake, restrained rats received tactile stimulation of the large whiskers (vibrissae) of the right side of the face, while a double-label 14C-autoradiographic study of local CMRglc (lCMRglc) and local CBF (lCBF) was performed. Unlesioned and unstimulated animals served as controls. In rats without frontal infarct, vibrissae stimulation led to activation of lCMRglc in the three synaptic relay stations of the barrel-field pathway (ipsilateral trigeminal medullary nucleus, contralateral ventrobasal thalamus, and contralateral barrel-field cortex). The mean increment in lCMRglc was 42% in lamina IV of barrel-field cortex and 49% in ventrobasal thalamus. Normalized lCBF tended to increase in superficial cortical laminae. In unstimulated animals with frontal infarct, lCMRglc was reduced by 20-30% throughout the ipsilateral barrel-field cortex as well as other ipsilateral cortical regions, but not in ventrobasal thalamus or other subcortical areas. In animals with frontal infarct subjected to contralateral vibrissae stimulation, a remarkable suppression of activation was observed throughout the barrel-field cortex so that left-less-than-right hemispheral lCMRglc asymmetry persisted despite stimulation. The ventrobasal thalamus, similarly, failed to increment its lCMRglc with vibrissae stimulation, whereas activation of the trigeminal nucleus was not suppressed. Similar trends were observed in the normalized lCBF data. These observations, which establish that a small frontal infarct is capable of suppressing normal physiological activation in remote ipsilateral brain structures, may have important implications with respect to suppression and recovery of function in human ischemic stroke.
J Cereb Blood Flow Metab 1989 Jun
PMID:Acute thrombotic infarction suppresses metabolic activation of ipsilateral somatosensory cortex: evidence for functional diaschisis. 271 5

A double-blind study was conducted in order to evaluate the effect of CDP-choline on functional recovery of hemiplegia. A standardized 12-grade scale (Hemiplegia Function Test) was utilized for the evaluation. The results indicate that for the upper limbs, doses of 1,000 and 250 mg of CDP-choline were superior to placebo at 8 weeks. The higher dose showed an effect at 4 weeks equal to that at 8 weeks while the effect of the lower dose was slower but reached the same level of effect as the higher dose at 8 weeks. Similar results were obtained for the lower limbs but the effectiveness was not statistically significant. The lesser effect for the lower limbs could be attributed to the relatively small number of patients in the early stages of recovery in the present series. No significant differences were found for the effects on subjective symptoms, neurological signs and overall judgment of the physicians. The findings suggest that CDP-choline promotes natural recovery in hemiplegia.
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PMID:Evaluation of the effect of CDP-choline on poststroke hemiplegia employing a double-blind controlled trial. Assessed by a new rating scale for recovery in hemiplegia. 700 29

Although preischemic hyperglycemia is known to aggravate damage due to transient ischemia, it is a matter of controversy whether or not this is a result of the exaggerated acidosis. It has recently been reported that although tissue acidosis of a comparable severity could be induced in normoglycemic dogs by an excessive rise in arterial CO2 tension, short-term functional recovery was improved, rather than compromised. In the present experiments we induced excessive hypercapnia (PaCO2, approximately 300 mm Hg) in normoglycemic rats before inducing forebrain ischemia of 10-min duration. This reduced the brain extracellular pH to values normally encountered in hyperglycemic rats subjected to ischemia. The events induced by hypercapnia clearly enhanced ischemic brain damage, as assessed histologically after 7 days of recovery. We hypothesize that the decisive event was an exaggerated decrease in extra- and intracellular pH and that the results thus demonstrate an adverse effect of acidosis. However, since postischemic seizures did not occur in the hypercapnic ischemic rats, the results also demonstrate that changes in intra-extracellular pH and bicarbonate concentrations modulated ischemic damage in an unexpected way.
J Cereb Blood Flow Metab 1994 Mar
PMID:Acidosis induced by hypercapnia exaggerates ischemic brain damage. 811 21

The consequences of an unilateral electrolytic entorhinal lesion on the functional activity in all major anatomically defined brain regions were evaluated in the rat. The 14C-2 deoxyglucose method served as a tool to quantify alterations of local cerebral glucose utilization (LCGU) ipsilateral and contralateral to the lesion at 4 days, 2 weeks, or 3 months after stereotaxic surgery. Apart from a few minor increases in the contralateral hemisphere, the predominant pattern consisted of reductions in the range of 10-40% in the ipsilateral hemisphere. Ipsilaterally, in extrahippocampal areas, LCGU had regained control levels at 2 weeks postlesion in contrast to hippocampal regions, where reductions were more pronounced than in other brain areas and partially persisted for up to 3 months. Interestingly, the termination zones of entorhinal fibers in the dentate gyrus did not regain control levels within 3 months. We conclude from the data that functional recovery of denervated primary target areas does not occur within 3 months after entorhinal lesions and that altered functional activity may be found beyond the primary target areas predominantly during the acute recovery period after the lesion. The data suggest that sprouting fibers do not reestablish a fully functional neuronal network during the recovery period.
J Cereb Blood Flow Metab 1996 Mar
PMID:Functional cerebral activity during regeneration from entorhinal lesions in the rat. 859 68

Treatments that postpone hypoxic spreading depression (SD)-like depolarization (also called anoxic depolarization) facilitate recovery of function after transient cerebral hypoxia. Hypertonia reduces cerebral excitability, and we tested whether it also offers protection against SD-like depolarization and hypoxia. Oxygen was withdrawn from hippocampal slices bathed in normal artificial cerebrospinal fluid (ACSF) and, simultaneously, from slices cut from the same hippocampus but bathed in strongly hypertonic ACSF. Extracellular osmolarity (pi(o)) was increased by adding 100 mM mannitol or fructose to ACSF. Slices in normal pi(o) underwent SD-like negative extracellular voltage shift (delta Vo). The hypertonic slices usually showed no SD-like delta Vo but only a small, gradual negative voltage shift. Hypertonia also prevented the precipitate drop of interstitial calcium level ([Ca2+]o). When oxygenation and normal osmolarity were restored, synaptic transmission in the previously hypertonic slices recovered completely, but 3 h after reoxygenation orthodromically transmitted population spikes of the control slices recovered only 25.1% of the initial control amplitude. We conclude that hypertonic treatment during hypoxia improves subsequent recovery of synaptic function. The protection is probably due to the prevention of calcium uptake by blocking the SD-like depolarization, with the prevention of hypoxic cell swelling playing a lesser role.
J Cereb Blood Flow Metab 1996 May
PMID:Hypertonic environment prevents depolarization and improves functional recovery from hypoxia in hippocampal slices. 862 50

Poly(ADP-ribose)polymerase (PARP, EC 2.4.2.30), an abundant nuclear protein activated by DNA nicks, mediates cell death in vitro by nicotinamide adenine dinucleotide (NAD) depletion after exposure to nitric oxide. The authors examined whether genetic deletion of PARP (PARP null mice) or its pharmacologic inhibition by 3-aminobenzamide (3-AB) attenuates tissue injury after transient cerebral ischemia. Twenty-two hours after reperfusion following 2 hours of filamentous middle cerebral artery occlusion, ischemic injury was decreased in PARP-/- and PARP+/- mice compared with PARP+/+ litter mates, and also was attenuated in 129/SV wild-type mice after 3-AB treatment compared with controls. Infarct sparing was accompanied by functional recovery in PARP-/- and 3-AB-treated mice. Increased poly(ADP-ribose) immunostaining observed in ischemic cell nuclei 5 minutes after reperfusion was reduced by 3-AB treatment. Levels of NAD--the substrate of PARP--were reduced 2 hours after reperfusion and were 35% of contralateral levels at 24 hours. The decreases were attenuated in PARP-/- mice and in 3-AB-treated animals. Poly(ADP-ribose)polymerase cleavage by caspase-3 (CPP-32) has been proposed as an important step in apoptotic cell death. Markers of apoptosis, such as oligonucleosomal DNA damage, total DNA fragmentation, and the density of terminal deoxynucleotidyl transferase dUTP nick-end-labelled (TUNEL +) cells, however, did not differ in ischemic brain tissue of PARP-/- mice or in 3-AB-treated animals versus controls, although there were differences in the number of TUNEL-stained cells reflecting the decrease in infarct size. Thus, ischemic brain injury activates PARP and contributes to cell death most likely by NAD depletion and energy failure, although the authors have not excluded a role for PARP in apoptotic cell death at earlier or later stages in ischemic cell death. Inhibitors of PARP activation could provide a potential therapy in acute stroke.
J Cereb Blood Flow Metab 1997 Nov
PMID:Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase. 939 Jun 45

We examined the nature and the selectivity of the motion deficits produced by lesions of extrastriate areas MT and MST. Lesions were made by injecting ibotenic acid into the representation of the left visual field in two macaque monkeys. The monkeys discriminated two stimuli that differed either in stimulus direction or orientation. Direction and orientation discrimination were assessed by measuring thresholds with gratings and random-dots placed in the intact or lesioned visual fields. At the start of behavioral testing, we found pronounced, motion-specific deficits in thresholds for all types of moving stimuli, including pronounced elevations in contrast thresholds and in signal-to-noise thresholds measured with moving gratings, as well as deficits in direction range thresholds and motion coherence measured with random-dot stimuli. In addition, the accuracy of direction discrimination was reduced at smaller spatial displacements (i.e. step sizes), suggesting an increase in spatial scale of the residual directional mechanism. Subsequent improvements in thresholds were seen with all motion stimuli, as behavioral training progressed, and these improvements occurred only with extensive behavioral testing in the lesioned visual field. These improvements were particularly pronounced for stimuli not masked by noise. On the other hand, deficits in the ability to extract motion from noisy stimuli and in the accuracy of direction discrimination persisted despite extensive behavioral training. These results demonstrate the importance of areas MT and MST for the perception of motion direction, particularly in the presence of noise. In addition, they provide evidence for the importance of behavioral training for functional recovery after cortical lesions. The data also strongly support the idea of functional specialization of areas MT and MST for motion processing.
Cereb Cortex
PMID:Transient and permanent deficits in motion perception after lesions of cortical areas MT and MST in the macaque monkey. 1002 98

Contrary to previous dogmas, it is now well established that brain cells can produce cytokines and chemokines, and can express adhesion molecules that enable an in situ inflammatory reaction. The accumulation of neutrophils early after brain injury is believed to contribute to the degree of brain tissue loss. Support for this hypothesis has been drawn from many studies where neutrophil-depletion blockade of endothelial-leukocyte interactions has been achieved by various techniques. The inflammation reaction is an attractive pharmacologic opportunity, considering its rapid initiation and progression over many hours after stroke and its contribution to evolution of tissue injury. While the expression of inflammatory cytokines that may contribute to ischemic injury has been repeatedly demonstrated, cytokines may also provide "neuroprotection" in certain conditions by promoting growth, repair, and ultimately, enhanced functional recovery. Significant additional basic work is required to understand the dynamic, complex, and time-dependent destructive and protective processes associated with inflammation mediators produced after brain injury. The realization that brain ischemia and trauma elicit robust inflammation in the brain provides fertile ground for discovery of novel therapeutic agents for stroke and neurotrauma. Inhibition of the mitogen-activated protein kinase (MAPK) cascade via cytokine suppressive anti-inflammatory drugs, which block p38 MAPK and hence the production of interleukin-1 and tumor necrosis factor-alpha, are most promising new opportunities. However, spatial and temporal considerations need to be exercised to elucidate the best opportunities for selective inhibitors for specific inflammatory mediators.
J Cereb Blood Flow Metab 1999 Aug
PMID:Inflammatory mediators and stroke: new opportunities for novel therapeutics. 1045 89

Early overuse of a lesioned forelimb, induced by immediate immobilization of the intact forelimb after a cortical lesion, has been reported to increase tissue damage and delay functional recovery. To investigate if early training without immobilization of the intact forelimb could increase tissue loss and reduce recovery, the middle cerebral artery was ligated distal to the striatal branches in 25 male spontaneously hypertensive rats. Control rats were housed in standard cages, training rats were transferred to larger cages allowing various activities and received additional special training 1 hour a day starting either 24 hours or 7 days after the ligation. The rats were tested on a rotating pole, in a leg placement test, and in a water maze and they were killed 6 weeks after the ligation. Delayed training resulted in the best overall performance; however, both training groups performed better than standard rats on the rotating pole. The cortical infarct volume was larger in the early training group than in the other two groups (P < .005), possibly related to increased glutamate release and peri-infarct cortical hyperexcitability.
J Cereb Blood Flow Metab 1999 Sep
PMID:Early training may exacerbate brain damage after focal brain ischemia in the rat. 1047 51


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