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. · Nov 2006
Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy.
In the present study, we investigate the hypothesis that mitochondrial oxidative damage and dysfunction precede the onset of neuronal loss after controlled cortical impact traumatic brain injury (TBI) in mice. Accordingly, we evaluated the time course of post-traumatic mitochondrial dysfunction in the injured cortex and hippocampus at 30 mins, 1, 3, 6, 12, 24, 48, and 72 h after severe TBI. A significant decrease in the coupling of the electron transport system with oxidative phosphorylation was observed as early as 30 mins after injury, followed by a recovery to baseline at 1 h after injury. ⋯ These findings indicate that post-traumatic oxidative lipid and protein damage, mediated in part by peroxynitrite, occurs in mitochondria with concomitant ultrastructural damage and impairment of mitochondrial bioenergetics. The data also indicate that compounds which specifically scavenge peroxynitrite (ONOO(-)) or ONOO(-)-derived radicals (e.g. ONOO(-)+H(+) --> ONOOH --> (*)NO(2)+(*)OH) may be particularly effective for the treatment of TBI, although the therapeutic window for this neuroprotective approach might only be 3 h.
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J. Cereb. Blood Flow Metab. · Oct 2006
Chronic hydrocephalus-induced changes in cerebral blood flow: mediation through cardiac effects.
Decreased cerebral blood flow (CBF) in hydrocephalus is believed to be related to increased intracranial pressure (ICP), vascular compression as the result of enlarged ventricles, or impaired metabolic activity. Little attention has been given to the relationship between cardiac function and systemic blood flow in chronic hydrocephalus (CH). Using an experimental model of chronic obstructive hydrocephalus developed in our laboratory, we investigated the relationship between the duration and severity of hydrocephalus and cardiac output (CO), CBF, myocardial tissue perfusion (MTP), and peripheral blood flow (PBF). ⋯ Our results suggest that CH may have more of an influence on CO and CBF in the chronic stage than in the early condition, which was dominated by surgical effect. The cause of this late deterioration of cardiac function in hydrocephalus is uncertain, but may reflect cardiac regulation secondary to physiologic response or brain injury. The relationship between cardiac function and CBF should be considered in the pathophysiology and clinical treatment of CH.
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J. Cereb. Blood Flow Metab. · Jul 2006
Comparative StudyEffect of duration of osmotherapy on blood-brain barrier disruption and regional cerebral edema after experimental stroke.
Osmotherapy is the cornerstone of medical management for cerebral edema associated with large ischemic strokes. We determined the effect of duration of graded increases in serum osmolality with mannitol and hypertonic saline (HS) on blood-brain barrier (BBB) disruption and regional cerebral edema in a well-characterized rat model of large ischemic stroke. Halothane-anesthetized adult male Wistar rats were subjected to transient (2-h) middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. ⋯ Blood-brain barrier disruption was maximal in rats treated with 0.9% saline for 48 h, but did not correlate with increases in serum osmolality or treatment duration with osmotic agents. Treatment with 7.5% HS attenuated water content in the periinfarct regions and all subregions of the contralateral nonischemic hemisphere to a greater extent than mannitol did with no adverse effect on survival rates. These data show that (1) BBB integrity is not affected by the duration and degree of serum osmolality with osmotic agents, and (2) attenuation of increases in brain water content with HS to target levels >350 mOsm/L may have therapeutic implications in the treatment of cerebral edema associated with ischemic stroke.
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J. Cereb. Blood Flow Metab. · Jul 2006
Cerebral hyperperfusion after carotid endarterectomy is associated with preoperative hemodynamic impairment and intraoperative cerebral ischemia.
The aim of this study was to investigate whether postoperative hyperperfusion is associated with preoperative cerebral hemodynamic impairment due to chronic ischemia and with acute cerebral ischemia during clamping of the internal carotid artery (ICA) during carotid endarterectomy (CEA). Transcranial cerebral oxygen saturation (SO2) was monitored intraoperatively using near-infrared spectroscopy in 89 patients undergoing CEA for ipsilateral ICA stenosis (>70%). Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were also measured using single photon emission computed tomography (SPECT) before CEA. ⋯ Logistic regression analysis showed that reduced preoperative CVR and reduced SO2 during ICA clamping were significant independent predictors of the development of hyperperfusion immediately after CEA. In fact, all patients with reduced preoperative CVR and reduced SO2 during ICA clamping developed post-CEA hyperperfusion, and two of these patients developed cerebral hyperperfusion syndrome. These data suggest that development of cerebral hyperperfusion after CEA is associated with preoperative hemodynamic impairment and intraoperative cerebral ischemia.
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J. Cereb. Blood Flow Metab. · Jul 2006
Comparative StudyCerebral hemodynamics after contralateral carotid endarterectomy in patients with symptomatic and asymptomatic carotid occlusion: a 10-year follow-up.
We sought to investigate whether carotid endarterectomy (CEA) can achieve long-term cerebral hemodynamic improvement and reduce recurrence of cerebral ischemic events in symptomatic and asymptomatic patients with severe (>70%) carotid artery stenosis contralateral to carotid occlusion (CO). Thirty-nine patients with severe carotid lesion contralateral to CO were studied before (1 day) and after CEA (at 7 days, 1, 3 and 6 months, and then yearly thereafter). Collateral flow and cerebral vasomotor reactivity (VMR) were assessed by transcranial Doppler sonography (TCD). ⋯ No significant spontaneous VMR recovery was recorded in the control group. After the initial recovery, no significant change in VMR was observed in the surgical group or the control group during the follow-up. In conclusion, in patients with severe carotid stenosis, CEA contralateral to symptomatic and asymptomatic CO determines a durable cerebral hemodynamic improvement not only on the side of the CEA but also on the contralateral side, with no difference between symptomatic and asymptomatic patients.