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. · Apr 1999
An intrathecal bolus of cyclosporin A before injury preserves mitochondrial integrity and attenuates axonal disruption in traumatic brain injury.
Traumatic brain injury evokes multiple axonal pathologies that contribute to the ultimate disconnection of injured axons. In severe traumatic brain injury, the axolemma is perturbed focally, presumably allowing for the influx of Ca2+ and initiation of Ca2+ -sensitive, proaxotomy processes. Mitochondria in foci of axolemmal failure may act as Ca2+ sinks that sequester Ca2+ to preserve low cytoplasmic calcium concentrations. ⋯ Further, this mitochondrial protection translated into axonal protection in a second group of injured rats, whose brains were reacted with antibodies against amyloid precursor protein, a known marker of injured axons. Pretreatment with CsA significantly reduced the number of axons undergoing delayed axotomy, as evidenced by a decrease in the density of amyloid precursor protein-immunoreactive axons. Collectively, these studies demonstrate that CsA protects both mitochondria and the related axonal shaft, suggesting that this agent may be of therapeutic use in traumatic brain injury.
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J. Cereb. Blood Flow Metab. · Feb 1999
ReviewThe trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation.
Primary headache syndromes, such as cluster headache and migraine, are widely described as vascular headaches, although considerable clinical evidence suggests that both are primarily driven from the brain. The shared anatomical and physiologic substrate for both of these clinical problems is the neural innervation of the cranial circulation. Functional imaging with positron emission tomography has shed light on the genesis of both syndromes, documenting activation in the midbrain and pons in migraine and in the hypothalamic gray in cluster headache. ⋯ The data presented here review these developments in the physiology of the trigeminovascular system, which demand renewed consideration of the neural influences at work in many primary headaches and, thus, further consideration of the physiology of the neural innervation of the cranial circulation. We take the view that the known physiologic and pathophysiologic mechanisms of the systems involved dictate that these disorders should be collectively regarded as neurovascular headaches to emphasize the interaction between nerves and vessels, which is the underlying characteristic of these syndromes. Moreover, the syndromes can be understood only by a detailed study of the cerebrovascular physiologic mechanisms that underpin their expression.
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J. Cereb. Blood Flow Metab. · Oct 1998
Neuronal stress response and neuronal cell damage after cardiocirculatory arrest in rats.
Cardiocirculatory arrest is the most common clinical cause of global cerebral ischemia. We studied neuronal cell damage and neuronal stress response after cardiocirculatory arrest and subsequent cardiopulmonary resuscitation in rats. The temporospatial cellular reactions were assessed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining of DNA fragments, in situ hybridization (heat shock protein hsp70; immediate early genes c-fos and c-jun), and immunocytochemical (HSP70; and myeloperoxidase, specific marker of polymorphonuclear leukocytes [PMNL]) techniques. ⋯ The number of PMNL increased significantly at 6 hours and 7 days after cardiac arrest; PMNL were distributed disseminately and were not regionally associated with neuronal cell damage. The current data support the view that CA1 neurons might undergo an apoptosis-associated death after cardiac arrest, but PMNL are not directly involved in this process. The marked differences in the time course and the characteristics of TUNEL staining and the neuronal stress response in CA1 sector and TRN point to different mechanisms of neuronal injury in the two selectively vulnerable areas.
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J. Cereb. Blood Flow Metab. · Jul 1998
Diffusion-, T2-, and perfusion-weighted nuclear magnetic resonance imaging of middle cerebral artery embolic stroke and recombinant tissue plasminogen activator intervention in the rat.
Thrombolysis of embolic stroke in the rat was measured using diffusion (DWI)-, T2 (T2WI)-, and perfusion (PWI)-weighted magnetic resonance imaging (MRI). An embolus was placed at the origin of the middle cerebral artery (MCA) by injection of an autologous single blood clot via an intraluminal catheter placed in the intracranial segment of internal carotid artery. Rats were treated with a recombinant tissue plasminogen activator (rt-PA) 1 hour after embolization (n = 9) or were not treated (n = 15). ⋯ Significant correlations (r > or = 0.80, P < 0.05) were found between lesion volume measured 1 week after embolization and CBF and ADCw obtained 1 hour after injection of rt-PA. Within a coronal section of brain, MRI cluster analysis, which combines ADCw and T2 data maps, indicated a significant reduction (P < 0.05) in the lesion 24 hours after thrombolysis compared with nontreated animals. These data demonstrate that the values for CBF and ADCw obtained 1 hour after injection of rt-PA correlate with histologic outcome in the tissue, and that the beneficial effect of thrombolysis of an intracranial embolus by means of rt-PA is reflected in an increase of CBF and ADCw, a reduction in the increase of T2, and a reduction of the ischemic lesion size measured using MRI cluster analysis.
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J. Cereb. Blood Flow Metab. · Jun 1998
Randomized Controlled Trial Clinical TrialQuinolinic acid is increased in CSF and associated with mortality after traumatic brain injury in humans.
We tested the hypothesis that quinolinic acid, a tryptophan-derived N-methyl-D-aspartate agonist produced by macrophages and microglia, would be increased in CSF after severe traumatic brain injury (TBI) in humans, and that this increase would be associated with outcome. We also sought to determine whether therapeutic hypothermia reduced CSF quinolinic acid after injury. Samples of CSF (n = 230) were collected from ventricular catheters in 39 patients (16 to 73 years old) during the first week after TBI, (Glasgow Coma Scale [GCS] < 8). ⋯ There was a powerful association between time after TBI and increased quinolinic acid (P < 0.00001), and quinolinic acid was higher in patients who died than in survivors (P = 0.003). Age, gender, GCS, and treatment (32 degrees C versus 37 degrees C) did not correlate with CSF quinolinic acid. These data reveal a large increase in quinolinic acid concentration in CSF after TBI in humans and raise the possibility that this macrophage-derived excitotoxin may contribute to secondary damage.