Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Feb 2008
Emergency preservation and resuscitation with profound hypothermia, oxygen, and glucose allows reliable neurological recovery after 3 h of cardiac arrest from rapid exsanguination in dogs.
We have used a rapid induction of profound hypothermia (<10 degrees C) with delayed resuscitation using cardiopulmonary bypass (CPB) as a novel approach for resuscitation from exsanguination cardiac arrest (ExCA). We have defined this approach as emergency preservation and resuscitation (EPR). We observed that 2 h but not 3 h of preservation could be achieved with favorable outcome using ice-cold normal saline flush to induce profound hypothermia. ⋯ All but one dog in the O-groups remained comatose. Brain histopathology in the O-G+ was worse than the other three groups (P<0.05). We conclude that EPR induced with a flush solution containing oxygen and glucose allowed satisfactory recovery of neurological function after a 3 h of CA, suggesting benefit from substrate delivery during induction or maintenance of a profound hypothermic CA.
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J. Cereb. Blood Flow Metab. · Feb 2008
Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans.
Caffeine, the most widely consumed psychoactive drug and a weak adenosine receptor antagonist, can be neuroprotective or neurotoxic depending on the experimental model or neurologic disorder. However, its contribution to pathophysiology and outcome in traumatic brain injury (TBI) in humans is undefined. We assessed serial cerebrospinal fluid (CSF) concentrations of caffeine and its metabolites (theobromine, paraxanthine, and theophylline) by high-pressure liquid chromatography/ultraviolet in 97 ventricular CSF samples from an established bank, from 30 adults with severe TBI. ⋯ Increases in CSF concentrations of the caffeine metabolites theobromine and paraxanthine were also associated with favorable outcome (P=0.018 and 0.056, respectively). Caffeine and its metabolites are commonly detected in CSF in patients with severe TBI and in an exploratory assessment are associated with favorable outcome. We speculate that caffeine may be neuroprotective by long-term upregulation of adenosine A1 receptors or acute inhibition of A2a receptors.
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J. Cereb. Blood Flow Metab. · Jan 2008
Variability and fractal analysis of middle cerebral artery blood flow velocity and arterial blood pressure in subarachnoid hemorrhage.
Higher biologic systems operate far from equilibrium resulting in order, complexity, fluctuation of inherent parameters, and dissipation of energy. According to the decomplexification theory, disease is characterized by a loss of system complexity. We analyzed such complexity in patients after subarachnoid hemorrhage (SAH), by applying the standard technique of variability analysis and the novel method of fractal analysis to middle cerebral artery blood flow velocity (FV) and arterial blood pressure (ABP). ⋯ FV and ABP fluctuated markedly despite homeostatic control. A reduced variability of FV and ABP might indicate a loss of complexity and was associated with a less favorable outcome. Therefore, the decomplexification theory of illness may apply to SAH.
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J. Cereb. Blood Flow Metab. · Jan 2008
Validation of cerebral venous oxygenation measured using near-infrared spectroscopy and partial jugular venous occlusion in the newborn lamb.
Near-infrared spectroscopy combined with partial jugular venous occlusion (JVO) offers promise for determining cerebral venous saturation (CSvO(2)) in sick preterm infants, but has not been validated in the newborn brain or under conditions of hypoxaemia. We assessed the accuracy of the CSvO(2) estimate using cerebral venous oxygen saturation in superior sagittal sinus blood (SSSO(2)) as the 'gold standard'. Comparisons were made in seven newborn lambs over a wide range of arterial oxygen saturations (SaO(2)) of 20% to 100%. ⋯ We conclude that the accuracy of estimating CSvO(2) varies with the DeltaCBV induced by JVO. Potential differences of optical properties between the head of the lamb and the human infant suggest that caution be exercised in directly applying these data to the human newborn. Nevertheless, this critical aspect of the JVO technique needs to be taken into consideration in developing an accurate measurement for sick preterm human infants.
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J. Cereb. Blood Flow Metab. · Jan 2008
Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke.
The 70-kDa heat shock protein (Hsp70) is involved in protecting the brain from a variety of insults including stroke. Although the mechanism has been largely considered to be because of its chaperone functions, recent work indicates that Hsp70 also modulates inflammatory responses. To explore how and whether Hsp70 regulate immune responses in brain ischemia, mice overexpressing Hsp70 (Hsp Tg) were subjected to 2 h middle cerebral artery occlusion, followed by 24 h reperfusion. ⋯ This was associated with decreased phosphorylation of NF-kappaB inhibitor protein, IkappaBalpha, and decreased expression of several NFkappaB-regulated genes. Co-immunoprecipitation studies revealed an interaction of Hsp70 with NF-kappaB and IkappaBalpha, but not with IkappaB kinase, IKKgamma, suggesting that Hsp70 binds to the NF-kappaB:IkappaB complex preventing IkappaB phosphorylation by IKK. The findings of the present work establish an anti-inflammatory role for Hsp70 in the context of brain ischemia as a novel mechanism of protection.