Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
-
J. Cereb. Blood Flow Metab. · Sep 2005
SOD1 overexpression and female sex exhibit region-specific neuroprotection after global cerebral ischemia due to cardiac arrest.
Cardiac arrest is often associated with poor neurologic outcome since therapeutic options are limited. We tested the hypothesis that overexpression of CuZn superoxide dismutase (SOD+/-) is neuroprotective in a new murine model of cardiac arrest and cardiopulmonary resuscitation (CPR). Second, we investigated if female and male mice sustain similar injury and if sex-specific outcomes are altered by SOD overexpression. ⋯ Comparison of hippocampal injury between genotypes revealed no differences for either males or females. In conclusion, SOD1 overexpression and female sex were associated with significant neuroprotection in this murine cardiac arrest model. However, no additive neuroprotection was observed, and these beneficial effects were restricted to specific brain regions.
-
J. Cereb. Blood Flow Metab. · Aug 2005
General anesthesia improves fetal cerebral oxygenation without evidence of subsequent neuronal injury.
Anesthetic exposure during pregnancy is viewed as a relatively routine medical practice. However, recent rodent studies have suggested that common anesthetic agents can damage the developing brain. Here we assessed this claim in a higher order species by exposing previously instrumented near-term pregnant sheep at gestational day 122 (+/-1) to a combination of midazolam, sodium thiopental, and isoflurane at clinically relevant doses and means of anesthetic delivery (i.e., active ventilation). ⋯ Postexposure monitoring failed to identify changes in physiologic status that could be injurious to the fetal brain. Finally, through the histologic assessment of noninstrumented sheep at the same gestational time point, we found no evidence for a direct fetal neuro-toxic effect of our triple-drug regimen. Collectively, these results appear to corroborate the presumed safety of inhalational anesthetic use during pregnancy.
-
J. Cereb. Blood Flow Metab. · Jul 2005
Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse.
Previous studies suggest that delayed neuronal death occurs in patients with inflicted traumatic brain injury (TBI) from child abuse. It is unknown whether the mode of this delayed neuronal death represents apoptosis or necrosis, a distinction that carries therapeutic ramifications. Cytochrome c, an electron transport chain component, can be released from mitochondria under conditions of cellular stress, whereupon it can initiate and serve as a biomarker of apoptosis. ⋯ These data suggest that apoptosis, as detected by the presence of cytochrome c in CSF, is uniquely prominent among the subset of TBI patients diagnosed with child abuse. The degree of apoptosis after TBI also appears to be gender-dependent. Development of strategies targeting apoptosis after TBI, particularly in victims of child abuse and in girls, appears justified.
-
J. Cereb. Blood Flow Metab. · Jun 2005
Clinical TrialMetabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study.
Brain trauma is accompanied by regional alterations of brain metabolism, reduction in metabolic rates and possible energy crisis. We hypothesize that microdialysis markers of energy crisis are present during the critical period of intensive care despite the absence of brain ischemia. In all, 19 brain injury patients (mean GCS 6) underwent combined positron emission tomography (PET) for metabolism of glucose (CMRglu) and oxygen (CMRO(2)) and cerebral microdialysis (MD) at a mean time of 36 h after injury. ⋯ In the region of the MD probe, PET imaging revealed ischemia in a single patient despite increased LPR in other patients. Lactate/pyruvate ratio correlated negatively with CMRO(2) (P < 0.001), but not with OEF or CvO(2). Traumatic brain injury leads to a state of persistent metabolic crisis as reflected by abnormal cerebral microdialysis LPR that is not related to ischemia.
-
J. Cereb. Blood Flow Metab. · May 2005
Monocyte chemoattractant protein-1 regulation of blood-brain barrier permeability.
The present study was designed to elucidate the effects of the chemokine monocyte chemoattractant protein (MCP-1) on blood-brain barrier (BBB) permeability. Experiments were conducted under in vitro conditions (coculture of brain endothelial cells and astrocytes) to study the cellular effects of MCP-1 and under in vivo conditions (intracerebral and intracerebroventricular administration of MCP-1) to study the potential contribution of MCP-1 to BBB disruption in vivo. Our results showed that MCP-1 induces a significant increase in the BBB permeability surface area product for fluorescein isothiocyanate (FITC)-albumin under in vivo conditions, particularly during prolonged (3 or 7 days) exposure (0.096+/-0.008 versus 0.031+/-0.005 microL/g min in controls at 3 days, P<0.001). ⋯ Monocytes/macrophages also participate in MCP-1-induced alterations in BBB permeability in vivo. Monocytes/macrophages depletion (by clodronate liposomes) reduced the effect of MCP-1 on BBB permeability in vivo approximately 2 fold. Our results suggest that, besides its main function of recruiting leukocytes at sites of inflammation, MCP-1 also plays a role in 'opening' the BBB.