Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rats with incomplete cerebral ischemia the effects of 70% N2O alone, isoflurane alone (0.5 and 1 MAC), and the combination of N2O + isoflurane on neurologic outcome, neurohistopathology, and EEG were compared. Moderate and severe ischemia were produced by right carotid artery occlusion combined with hemorrhagic hypotension (moderate ischemia, MAP = 30 mmHg, FIO2 = 0.30; severe ischemia, MAP = 25 mmHg, FIO2 = 0.20). Neurologic outcome was evaluated using a graded deficit score from 0 to 5 (0 = normal, 5 = death associated with stroke), and neurohistopathology was evaluated using a 40-point scale from 0 = normal to 40 = total hemisphere infarct at the level of the caudate nucleus in coronal section. Compared with N2O alone, isoflurane (0.5 and 1 MAC) improved neurologic outcome following moderate ischemia (P less than 0.05). Isoflurane also decreased histopathologic damage following moderate ischemia (N2O control = 33 +/- 1 vs. 0.5 MAC isoflurane = 11 +/- 4 and 1 MAC isoflurane = 12 +/- 3, P less than 0.05), whereas only 0.5 MAC isoflurane decreased histopathologic damage following severe ischemia (N2O control = 38 +/- 1 vs. 0.5 MAC isoflurane = 25 +/- 5; P less than 0.05) Adding N2O to 0.5 MAC isoflurane attenuated the neurologic protective effect of isoflurane alone and increased histopathologic damage following both moderate and severe ischemia (moderate = 23 +/- 5, severe = 37 +/- 2; both P greater than 0.05 compared with N2O controls). The effect of adding 70% N2O to isoflurane on cerebral blood flow (CBF) and cerebral oxygen consumption(CMRO2) was also evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The interaction of nitrous oxide and isoflurane with incomplete cerebral ischemia in the rat. 271 9

Nimodipine is a calcium slow channel blocker with several pharmacologic properties suggesting the potential to favorably modify outcome in focal cerebral ischemia. Thirty adult cats underwent unilateral middle cerebral artery (MCA) occlusion for 4 hours. Seventeen cats were treated with an ipsilateral intracarotid infusion of nimodipine (1 microgram kg-1 min -1) beginning 15 minutes before MCA occlusion and continuing throughout the occlusion period. Eight nimodipine treated cats maintaining MAP greater than 90 mmHg were assigned to a Higher Pressure Nimodipine (HPN) group. The remaining nine treated cats with MAP less than 90 mmHg were assigned to the Lower Pressure Nimodipine (LPN) group. Thirteen cats were untreated, receiving an isovolumetric amount of vehicle through the ipsilateral carotid artery. Local cerebral blood flow (ICBF) was continuously monitored using thermal diffusion probes. The brains, assessed for colloidal carbon perfusion, fluorescein and Evans blue staining, electroencephalographic activity (EEG), and histological changes, revealed no significant differences by any of these methods between the HPN and control animals with the exceptions of: HPN treated cats exhibited a preservation of EEG activity at 15 minutes post-occlusion compared to the untreated cats, and Post-ischemic surface colloidal carbon perfusion was better preserved in the treated cats than in the untreated cats. Mild hypotension, as demonstrated by the LPN group, negated these two positive effects. Prior to MCA occlusion, ICBF was bilaterally significantly increased after nimodipine infusion in the HPN group as compared to vehicle infusion. Intra-arterially infused nimodipine did not reduce infarct size.
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PMID:Effects of nimodipine on acute focal cerebral ischemia. 376 59

Monitoring of ICP from the subarachnoid, intraparenchymal, or ventricular spaces can be accomplished easily and reliably. The risks and benefits of each approach should be considered when choosing the monitoring technique. The goal of ICP management is to prevent herniation and to optimize cerebral perfusion. Even transient episodes of post-traumatic cerebral ischemia due to inadequate CPP can quickly nullify all resuscitative efforts. The provision of sufficient CBF is complicated by the varying degree of disruption of pressure autoregulation commonly resulting from head trauma. Post-injury, there is a need to provide a CPP which is elevated to some extent with respect to that sufficient in uninjured brains. This generally requires a CPP of at least 70 mm Hg, which must be accomplished by maintaining an adequate MAP while controlling ICH. Although ICH can generally be controlled using methods commonly employed, the majority of these techniques have potential complications. Additionally, there is increasing evidence that significant variation exists in the pathologic processes driving ICH in individual patients. Therefore, goals such as the desired CPP and conditions such as the relative contribution of edema, cerebral hypervolemia, and ischemia to ICH should optimally be considered in a patient-specific fashion and allow a targeted approach to therapy.
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PMID:Intracranial pressure. Monitoring and management. 782 72

Lesion and focal cerebral ischemia of the insular cortex (IC) results in elevated renal sympathetic nerve activity (RSNA) and arterial pressure (AP) in the Wistar rat, while the opposite effect is observed in the spontaneously hypertensive rat (SHR). Acute changes in AP, heart rate (HR) and RSNA were measured in propofol-anesthetized and conscious SHR (n = 17) and Wistar rats (n = 17) during pressure injection of D,L-homocysteic acid (DLH; 100 mM) and lidocaine (LID; 20 mg/ml) into the IC. DLH injections (200 nl) into the IC of anesthetized Wistar rats resulted in a significant increase in MAP (mean change = +27 +/- 7 mmHg; P < 0.05) and a significant decrease in HR (-22 +/- 9 beats/min) and RSNA (-11 +/- 4 microV.s). Neither DLH nor LID injections into the IC of anesthetized SHR affected MAP or RNA. DLH and LID injections (500 nl) into the IC of conscious Wistar rats both resulted in a significant increase in MAP (+26 +/- 5 mmHg; 11 +/- 4 mmHg, respectively). Neither DLH nor LID injections had any cardiovascular effects in the conscious SHR. It therefore appears that the IC of conscious Wistar rats has a tonic inhibitory output, while neural excitation is capable of eliciting pressor responses. Conversely, the IC of SHR appears to exert no tonic influence on MAP.
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PMID:Autonomic responses of the insular cortex in hypertensive and normotensive rats. 784 Mar 24

The goal of therapy in patients with severe head injury is to avoid secondary brain damage. Analgesia and sedation are an essential part of the therapy, and several drugs are in current use. However, few controlled clinical trials have been performed so far, and none of these drugs has proved to be superior. Although in the past the therapy has been focused on controlling elevated intracranial pressure (ICP), many authors emphasize the role of cerebral ischaemia in the prognosis of patients. Therefore, cerebral perfusion pressure (CPP) i.e. the difference between ICP and mean arterial pressure (CPP = MAP-ICP), seems to be more important than ICP alone. Analgesics and sedatives reduce the cerebral metabolic rate (CMR), and the consequent decrease in cerebral oxygen uptake might prevent ischaemic damage in regions with low perfusion. Moreover, a decrease in CMR is often associated with a decrease of cerebral blood flow (CBF) in regions with normal perfusion and, as a result, ICP is also reduced. Basically, the cerebral effects (on ICP, CMR, and CBF) and the haemodynamic effects with respect to maintenance of a sufficient CPP are most important in the selection of drugs for analgosedation. In addition, the effects on general intensive care management must be considered (pulmonary function, immunreactivity bowel motility). The purpose of this paper is to describe drugs commonly used for analgosedation in severe head injury. Barbiturates bring about the most pronounced decrease of CMR and ICP. In the past these drugs were used routinely in high doses ("barbiturate coma"). However, no improvement in outcome was demonstrable, and vitally dangerous side effects, such as infection, pulmonary dysfunction, arterial hypotension, and renal failure often occurred. High-dose barbiturate therapy is therefore only indicated in exceptional cases, such as refractory increase in ICP with preserved CO2 response of cerebral vessels. The effect is dependent on CMR at the start of this therapy. Benzodiazepines are frequently used in patients with head injury. They cause only a moderate decrease of CMR and ICP. In general, side effects are negligible. However, a possible decrease of MAP by reduced central sympathetic drive has to be taken into account. Opioids are also frequently used in patients with head trauma. The observed cerebral effects are inconsistent. Some authors have described increases in ICP, CBF, and CMR, but in most studies no influence on these values, or a decrease, has been observed. In any case, cautious titration of these drugs and cerebral monitoring are therefore desirable. As with benzodiazepines, a decrease in MAP due to central effects is possible. In addition, opioids inhibit bowel motility. Ketamine is generally used because of its favourable circulatory effects, bronchodilatation and absence of inhibition of bowel motility. In patients with increased ICP, however, it is often considered contraindicated, since it can be associated with cerebral vasodilation and ICP increase. Other studies did not confirm an increase of ICP when controlled ventilation and additional sedation were applied. More recent studies have demonstrated the role of neuroexcitatory NMDA-receptors in ischaemic and traumatic brain damage. Since ketamine exerts an antagonistic effect on N-methyl-D-aspartate receptors (NMDA) and studies in animals have demonstrated a protective effect of ketamine against ischaemic and traumatic brain damage, controlled clinical studies in patients with head injury are desirable. Propofol results in a profound decrease of CMR and a significant decrease of ICP, but often also in haemodynamic depression. Few results obtained during long-term administration are available, but it seems to be beneficial. More clinical studies are warranted. Gamma-hydroxybutyrate (GHB) is a physiological substance, which has only sporadically been investigated for sedation in patients with head trauma. The few available studies show beneficial res
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PMID:[Analgesia and sedation in patients with head-brain trauma]. 859 67

Cytosolic Ca2+ overload has been proposed as a main cause of neuronal injury during cerebral ischemia. SNX-111, a synthetic product of the naturally occurring omega-conotoxin MVIIA, is a novel, presynaptic N-type Ca2+ channel antagonist and has been reported to be neuroprotective against cerebral ischemia. We studied the neuroprotective effects of SNX-111 in a rabbit model of focal cerebral ischemia. New Zealand white male rabbits (2.5-3.5 kg) were given 1 mg/kg/h i.v. SNX-111 (n=8) or normal saline (n=8) 10 min after onset of a 2-h period of transient focal cerebral ischemia induced by occlusion of the left middle cerebral, anterior cerebral and internal carotid arteries followed by 4 h reperfusion. SNX-111 significantly attenuated overall cortical ischemic neuronal damage by 44% (saline, 38.7+/-3.0%; SNX-111, 21.5+/-6.0%, P<0.05) and regions of hyperintensity on T2-weighted MRI by 30% (saline, 70.6+/-4.0%; SNX-111, 49.3+/-11.0%, P<0.05). No significant difference in (regional cerebral blood flow) rCBF or MAP (mean arterial blood pressure) was found between SNX-111- and saline-treated rabbits suggesting that neuroprotection is due to a cellular effect. We conclude that SNX-111 reduces ischemic injury in this model. Its use as a clinical neuroprotective agent for cerebrovascular surgery or stroke should be investigated further.
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PMID:SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits. 945 74

Cortical spreading depression (CSD) has been shown to have neuroprotective effects when administered in advance of cerebral ischemia. The mechanism by which CSD induces its neuroprotective effect however remains to be elucidated. Since MAP kinases have been shown to impart neuroprotection in ischemic preconditioning paradigms, we attempted to determine the role CSD may have in the activation of MAPK. We show that CSD is capable of increasing the phosphorylation of ERK in a MEK-dependent manner. This phosphorylation is, however, transient, as phosphorylated ERK levels return to control levels 45 min after 2 h of CSD elicitation. Immunohistochemical analysis reveals that the phosphorylated form of ERK is located ubiquitously in cells of the CSD-treated cortex while CSD-elicited MEK phosphorylation resides solely in the nuclei. These data suggest that CSD may act via the MAP kinase pathways to mediate preconditioning.
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PMID:Cortical spreading depression transiently activates MAP kinases. 1186 11

In the present study, we attempted to assess the mechanisms underlying the neuroprotective effect of hypervolaemic haemodilution in rat heatstroke. In anaesthetized rats treated with normal saline (NS) immediately after the onset of heatstroke induced by T (a) (ambient temperature) of 42 degrees C for 88 min, followed by T (a) of 24 degrees C for 12 min, the values for MAP (mean arterial pressure), ICP (intracranial pressure), CPP (cerebral perfusion pressure), CBF (cerebral blood blow), brain P O(2) (partial pressure of O(2)) and striatal glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score were 42+/-3 mmHg, 33+/-3 mmHg, 9+/-3 mmHg, 109+/-20 BPU (blood perfusion units), 6+/-1 mmHg, 51+/-7 micromol/l, 24+/-3 micromol/l, 124+/-32, 694+/-22% of baseline and 2.25+/-0.05 respectively. In animals treated with 10% albumin immediately after the onset of heatstroke ( T (a) of 42 degrees C for 88 min), the values for MAP, ICP, CPP, CBF, brain P O(2) and striatal glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score were 64+/-6 mmHg, 10+/-2 mmHg, 54+/-5 mmHg, 452+/-75 BPU, 15+/-2 mmHg, 3+/-2 micromol/l, 4+/-2 micromol/l, 7+/-3, 119+/-7% of baseline and 0.38+/-0.05 respectively. Apparently, the heatstroke-induced arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischaemia, brain hypoxia, increased levels of striatal glutamate, glycerol, lactate/pyruvate ratio and hydroxyl radicals, and increased striatal neuronal damage score values were all attenuated significantly by the induction of hypervolaemic haemodilution in rats immediately at the onset of heatstroke. These results demonstrate that the neuroprotective effect of hypervolaemic haemodilution is associated with a decrease in the elevation of glutamate, glycerol, lactate and free radicals in brain exposed to experimental heatstroke-induced cerebral ischaemia/hypoxia injury.
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PMID:Effect of hypervolaemic haemodilution on cerebral glutamate, glycerol, lactate and free radicals in heatstroke rats. 1468 77

The link between membrane phospholipids and different intracellular signal transduction pathways affected by cerebral ischaemia is unclear. CDP-choline, a major neuronal membrane lipid precursor and its intracellular target proteins and transcription factors were studied to further understand its role in ischaemic stroke. Cerebral ischaemia was produced by distal, permanent occlusion of the middle cerebral artery (MCAO) in the rat. Animals receiving 500 mg/kg of CDP-choline in 0.5 ml of 0.9% saline, intraperitoneally, 24 h and 1 h before MCAO and 23 h after MCAO demonstrated a notable reduction in the phosphorylation of MAP-kinase family members, ERK1/2 and MEK1/2, as well as Elk-1 transcription factor, compared with control animals treated with 0.5 ml of 0.9% saline. Immunohistochemistry showed a particular reduction in immunoreactivity in glia. The effects of CDP-choline on intracellular mechanisms of signal transduction, suggests that this molecule may play a key role in recovery after ischaemic stroke.
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PMID:Citicoline inhibits MAP kinase signalling pathways after focal cerebral ischaemia. 1625 56

Although stem cell-based treatments for stroke and other neurodegenerative diseases have advanced rapidly, there are still few clinical treatments available. In this study, rats receiving intracerebral peripheral blood hematopoietic stem cell (CD34+) (PBSC) transplantation showed much more improvement in neurological function after chronic cerebral ischemia in comparison with vehicle-treated control rats. Using laser-scanning confocal microscopy, implanted PBSCs were seen to differentiate into glial cells [GFAP+ (glial fibrillary acidic protein-positive)], neurons [Nestin+, MAP-2+ (microtubule-associated protein 2-positive), Neu-N+ (neuronal nuclear antigen-positive)], and vascular endothelial cells [vWF+ (von Willebrand factor-positive)], thereby enhancing neuroplastic effects in the ischemic brain. Cortical neuronal activity, as evaluated by 1H-MRS (proton magnetic resonance spectroscopy), also increased considerably in PBSC-treated rats compared with a vehicle-treated control group. In addition, PBSC implantation promoted the formation of new vessels, thereby increasing the local cortical blood flow in the ischemic hemisphere. These observations may be explained by the involvement of stem cell-derived macrophage/microglial cells, and beta1 integrin expression, which might enhance this angiogenic architecture over the ischemic brain. Furthermore, quantitative reverse transcription-PCR analysis showed significantly increased modulation of neurotrophic factor expression in the ischemic hemisphere of the PBSC-transplanted rats compared with vehicle-treated control rats. Thus, intracerebral PBSC transplantation might have potential as a therapeutic strategy for treating cerebrovascular diseases.
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PMID:Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic stroke rats. 1657 51


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