Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage?

View More View Less
  • 1 Department of Neurology and Physiology, Charité, Humboldt-University, Berlin, Germany; Laboratory of Experimental Neurocytology, Brain Research Institute, Moscow, Russia; and Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

Object. The pathogenesis of delayed ischemic neurological deficits after subarachnoid hemorrhage has been related to products of hemolysis. Topical brain superfusion of artificial cerebrospinal fluid (ACSF) containing the hemolysis products K+ and hemoglobin (Hb) was previously shown to induce ischemia in rats. Superimposed on a slow vasospastic reaction, the ischemic events represent spreading depolarizations of the neuronal—glial network that trigger acute vasoconstriction. The purpose of the present study was to investigate whether such spreading ischemias in the cortex lead to brain damage.

Methods. A cranial window was implanted in 31 rats. Cerebral blood flow (CBF) was measured using laser Doppler flowmetry, and direct current (DC) potentials were recorded. The ACSF was superfused topically over the brain. Rats were assigned to five groups representing different ACSF compositions. Analyses included classic histochemical and immunohistochemical studies (glial fibrillary acidic protein and ionized calcium binding adaptor molecule) as well as a terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling assay.

Superfusion of ACSF containing Hb combined with either a high concentration of K+ (35 mmol/L, 16 animals) or a low concentration of glucose (0.8 mmol/L, four animals) reduced CBF gradually. Spreading ischemia in the cortex appeared when CBF reached 40 to 70% compared with baseline (which was deemed 100%). This spreading ischemia was characterized by a sharp negative shift in DC, which preceded a steep CBF decrease that was followed by a slow recovery (average duration 60 minutes). In 12 of the surviving 14 animals widespread cortical infarction was observed at the site of the cranial window and neighboring areas in contrast to findings in the three control groups (11 animals).

Conclusions. The authors conclude that subarachnoid Hb combined with either a high K+ or a low glucose concentration leads to widespread necrosis of the cortex.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address reprint requests to: Jens P. Dreier, M.D., Department of Neurology, Charité Hospital, Humboldt University, 10098 Berlin, Germany. email: jens.dreier@charite.de.
  • 1.

    Astrup J, & Norberg K: Potassium activity in cerebral cortex in rats during progressive severe hypoglycemia. Brain Res 103:418423, 1976 Astrup J, Norberg K: Potassium activity in cerebral cortex in rats during progressive severe hypoglycemia. Brain Res 103:418–423, 1976

    • Search Google Scholar
    • Export Citation
  • 2.

    Avoli M, , Drapeau C, & Louvel J, et al: Epileptiform activity induced by low extracellular magnesium in the human cortex maintained in vitro. Ann Neurol 30:589596, 1991 Avoli M, Drapeau C, Louvel J, et al: Epileptiform activity induced by low extracellular magnesium in the human cortex maintained in vitro. Ann Neurol 30:589–596, 1991

    • Search Google Scholar
    • Export Citation
  • 3.

    Back T, , Kohno K, & Hossmann KA: Cortical negative DC deflections following middle cerebral artery occlusion and KCl-induced spreading depression: effect on blood flow, tissue oxygenation, and electroencephalogram. J Cereb Blood Flow Metab 14:1219, 1994 Back T, Kohno K, Hossmann KA: Cortical negative DC deflections following middle cerebral artery occlusion and KCl-induced spreading depression: effect on blood flow, tissue oxygenation, and electroencephalogram. J Cereb Blood Flow Metab 14:12–19, 1994

    • Search Google Scholar
    • Export Citation
  • 4.

    Back T, , Nedergaard M, & Ginsberg MD: The ischemic penumbra: pathophysiology, and relevance of spreading depression-like phenomena, in Ginsberg MD, & Bogousslavsky J (eds): Cerebrovascular Disease. Pathophysiology, Diagnosis, and Treatment. Cambridge, MA: Blackwell Scientific, 1998, pp 276286 Back T, Nedergaard M, Ginsberg MD: The ischemic penumbra: pathophysiology, and relevance of spreading depression-like phenomena, in Ginsberg MD, Bogousslavsky J (eds): Cerebrovascular Disease. Pathophysiology, Diagnosis, and Treatment. Cambridge, MA: Blackwell Scientific, 1998, pp 276–286

    • Search Google Scholar
    • Export Citation
  • 5.

    Bogousslavsky J, , Regli F, & Van Melle G, et al: Migraine stroke. Neurology 38:223227, 1988 Bogousslavsky J, Regli F, Van Melle G, et al: Migraine stroke. Neurology 38:223–227, 1988

    • Search Google Scholar
    • Export Citation
  • 6.

    Broderick JP: Stroke and migraine, in Welch KMA, , Caplan LR, & Reis DJ, et al (eds): Primer on Cerebrovascular Diseases. San Diego: Academic Press, 1997, pp 333335 Broderick JP: Stroke and migraine, in Welch KMA, Caplan LR, Reis DJ, et al (eds): Primer on Cerebrovascular Diseases. San Diego: Academic Press, 1997, pp 333–335

    • Search Google Scholar
    • Export Citation
  • 7.

    Chebabo SR, , Hester MA, & Aitken PG, et al: Hypotonic exposure enhances synaptic transmission and triggers spreading depression in rat hippocampal tissue slices. Brain Res 695:203216, 1995 Chebabo SR, Hester MA, Aitken PG, et al: Hypotonic exposure enhances synaptic transmission and triggers spreading depression in rat hippocampal tissue slices. Brain Res 695:203–216, 1995

    • Search Google Scholar
    • Export Citation
  • 8.

    Dirnagl U, , Kaplan B, & Jacewicz M: Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model. J Cereb Blood Flow Metab 9:589596, 1989 Dirnagl U, Kaplan B, Jacewicz M: Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model. J Cereb Blood Flow Metab 9:589–596, 1989

    • Search Google Scholar
    • Export Citation
  • 9.

    Dreier JP, , Körner K, & Ebert N, et al: Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-l-arginine induce cortical spreading ischemia when K+ is increased in the subarachnoid space. J Cereb Blood Flow Metab 18:978990, 1998 Dreier JP, Körner K, Ebert N, et al: Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-l-arginine induce cortical spreading ischemia when K+ is increased in the subarachnoid space. J Cereb Blood Flow Metab 18:978–990, 1998

    • Search Google Scholar
    • Export Citation
  • 10.

    Dreier JP, , Körner K, & Görner A, et al: Nitric oxide modulates the CBF response to increased extracellular potassium. J Cereb Blood Flow Metab 15:914919, 1995 Dreier JP, Körner K, Görner A, et al: Nitric oxide modulates the CBF response to increased extracellular potassium. J Cereb Blood Flow Metab 15:914–919, 1995

    • Search Google Scholar
    • Export Citation
  • 11.

    Duckrow RB: A brief hypoperfusion precedes spreading depression if nitric oxide synthesis is inhibited. Brain Res 618:190195, 1993 Duckrow RB: A brief hypoperfusion precedes spreading depression if nitric oxide synthesis is inhibited. Brain Res 618:190–195, 1993

    • Search Google Scholar
    • Export Citation
  • 12.

    Edwards DH, , Byrne JV, & Griffith TM: The effect of chronic subarachnoid hemorrhage on basal endothelium-derived relaxing factor activity in intrathecal cerebral arteries. J Neurosurg 76:830837, 1992 Edwards DH, Byrne JV, Griffith TM: The effect of chronic subarachnoid hemorrhage on basal endothelium-derived relaxing factor activity in intrathecal cerebral arteries. J Neurosurg 76:830–837, 1992

    • Search Google Scholar
    • Export Citation
  • 13.

    Ferraro G, , Montalbano ME, & La Grutta V: Nitric oxide and glutamate interaction in the control of cortical and hippocampal excitability. Epilepsia 40:830836, 1999 Ferraro G, Montalbano ME, La Grutta V: Nitric oxide and glutamate interaction in the control of cortical and hippocampal excitability. Epilepsia 40:830–836, 1999

    • Search Google Scholar
    • Export Citation
  • 14.

    Garcia JH, , Liu KF, & Ho KL: Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 26:636643, 1995 Garcia JH, Liu KF, Ho KL: Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 26:636–643, 1995

    • Search Google Scholar
    • Export Citation
  • 15.

    Gorelova NA, , Koroleva VI, & Amemori T, et al: Ketamine blockade of cortical spreading depression in rats. Electroencephalogr Clin Neurophysiol 66:440447, 1987 Gorelova NA, Koroleva VI, Amemori T, et al: Ketamine blockade of cortical spreading depression in rats. Electroencephalogr Clin Neurophysiol 66:440–447, 1987

    • Search Google Scholar
    • Export Citation
  • 16.

    Hansen AJ, , Quistorff B, & Gjedde A: Relationship between local changes in cortical blood flow and extracellular K+ during spreading depression. Acta Physiol Scand 109:16, 1980 Hansen AJ, Quistorff B, Gjedde A: Relationship between local changes in cortical blood flow and extracellular K+ during spreading depression. Acta Physiol Scand 109:1–6, 1980

    • Search Google Scholar
    • Export Citation
  • 17.

    Hasan D, , Wijdicks EFM, & Vermeulen M: Hyponatremia is associated with cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Ann Neurol 27:106108, 1990 Hasan D, Wijdicks EFM, Vermeulen M: Hyponatremia is associated with cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Ann Neurol 27:106–108, 1990

    • Search Google Scholar
    • Export Citation
  • 18.

    Imai Y, , Ibata I, & Ito D, et al: A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun 224:855862, 1996 Imai Y, Ibata I, Ito D, et al: A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun 224:855–862, 1996

    • Search Google Scholar
    • Export Citation
  • 19.

    Kassell NF, , Torner JC, & Haley EC Jr, et al: The International Cooperative Study on the timing of aneurysm surgery. Part 1: Overall management results. J Neurosurg 73:1836, 1990 Kassell NF, Torner JC, Haley EC Jr, et al: The International Cooperative Study on the timing of aneurysm surgery. Part 1: Overall management results. J Neurosurg 73:18–36, 1990

    • Search Google Scholar
    • Export Citation
  • 20.

    Lauritzen M: Pathophysiology of the migraine aura. The spreading depression theory. Brain 117:199210, 1994 Lauritzen M: Pathophysiology of the migraine aura. The spreading depression theory. Brain 117:199–210, 1994

    • Search Google Scholar
    • Export Citation
  • 21.

    Lauritzen M, & Hansen AJ: The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab 12:223229, 1992 Lauritzen M, Hansen AJ: The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab 12:223–229, 1992

    • Search Google Scholar
    • Export Citation
  • 22.

    Lauritzen M, , Rice ME, & Okada Y, et al: Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum. Brain Res 475:317327, 1988 Lauritzen M, Rice ME, Okada Y, et al: Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum. Brain Res 475:317–327, 1988

    • Search Google Scholar
    • Export Citation
  • 23.

    Li Y, , Sharov VG, & Jiang N, et al: Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 146:10451051, 1995 Li Y, Sharov VG, Jiang N, et al: Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 146:1045–1051, 1995

    • Search Google Scholar
    • Export Citation
  • 24.

    Lillie RD (ed): Histopathologic Technic and Practical Histochemistry, ed 3. New York: Blakiston, 1965 Lillie RD (ed): Histopathologic Technic and Practical Histochemistry, ed 3. New York: Blakiston, 1965

    • Search Google Scholar
    • Export Citation
  • 25.

    Lipton SA, , Choi YB, & Pan ZH, et al: A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626632, 1993 Lipton SA, Choi YB, Pan ZH, et al: A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632, 1993

    • Search Google Scholar
    • Export Citation
  • 26.

    Macdonald RL, & Weir BKA: A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke 22:971982, 1991 Macdonald RL, Weir BKA: A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke 22:971–982, 1991

    • Search Google Scholar
    • Export Citation
  • 27.

    Manzoni O, , Prezeau L, & Marin P, et al: Nitric oxide-induced blockade of NMDA receptors. Neuron 8:653662, 1992 Manzoni O, Prezeau L, Marin P, et al: Nitric oxide-induced blockade of NMDA receptors. Neuron 8:653–662, 1992

    • Search Google Scholar
    • Export Citation
  • 28.

    McCulloch J, , Edvinsson L, & Watt P: Comparison of the effects of potassium and pH on the calibre of cerebral veins and arteries. Pflügers Arch 393:9598, 1982 McCulloch J, Edvinsson L, Watt P: Comparison of the effects of potassium and pH on the calibre of cerebral veins and arteries. Pflügers Arch 393:95–98, 1982

    • Search Google Scholar
    • Export Citation
  • 29.

    Menzies SA, , Hoff JT, & Betz AL: Middle cerebral artery occlusion in rats: a neurological and pathological evaluation of a reproducible model. Neurosurgery 31:100107, 1992 Menzies SA, Hoff JT, Betz AL: Middle cerebral artery occlusion in rats: a neurological and pathological evaluation of a reproducible model. Neurosurgery 31:100–107, 1992

    • Search Google Scholar
    • Export Citation
  • 30.

    Minato H, , Hashizume M, & Masuda Y, et al: Modulation of extraluminally induced vasoconstrictions by endothelium-derived nitric oxide in the canine basilar artery. Arzneimittelforschung 45:675678, 1995 Minato H, Hashizume M, Masuda Y, et al: Modulation of extraluminally induced vasoconstrictions by endothelium-derived nitric oxide in the canine basilar artery. Arzneimittelforschung 45:675–678, 1995

    • Search Google Scholar
    • Export Citation
  • 31.

    Moen M, , Levine SR, & Newman DS, et al: Bilateral posterior cerebral artery strokes in a young migraine sufferer. Stroke 19:525528, 1988 Moen M, Levine SR, Newman DS, et al: Bilateral posterior cerebral artery strokes in a young migraine sufferer. Stroke 19:525–528, 1988

    • Search Google Scholar
    • Export Citation
  • 32.

    Nedergaard M, & Astrup J: Infarct rim: effect of hyperglycemia on direct current potential and [14C]2-deoxyglucose phosphorylation. J Cereb Blood Flow Metab 6:607615, 1986 Nedergaard M, Astrup J: Infarct rim: effect of hyperglycemia on direct current potential and [14C]2-deoxyglucose phosphorylation. J Cereb Blood Flow Metab 6:607–615, 1986

    • Search Google Scholar
    • Export Citation
  • 33.

    Neil-Dwyer G, , Lang DA, & Doshi B, et al: Delayed cerebral ischaemia: the pathological substrate. Acta Neurochir 131:137145, 1994 Neil-Dwyer G, Lang DA, Doshi B, et al: Delayed cerebral ischaemia: the pathological substrate. Acta Neurochir 131:137–145, 1994

    • Search Google Scholar
    • Export Citation
  • 34.

    Nilsson OG, , Brandt L, & Ungerstedt U, et al: Bedside detection of brain ischemia using intracerebral microdialysis: subarachnoid hemorrhage and delayed ischemic deterioration. Neurosurgery 45:11761184, 1999 Nilsson OG, Brandt L, Ungerstedt U, et al: Bedside detection of brain ischemia using intracerebral microdialysis: subarachnoid hemorrhage and delayed ischemic deterioration. Neurosurgery 45:1176–1184, 1999

    • Search Google Scholar
    • Export Citation
  • 35.

    Nishiye E, , Nakao K, & Itoh T, et al: Factors inducing endothelium-dependent relaxation in the guinea-pig basilar artery as estimated from the actions of haemoglobin. Br J Pharmacol 96:645655, 1989 Nishiye E, Nakao K, Itoh T, et al: Factors inducing endothelium-dependent relaxation in the guinea-pig basilar artery as estimated from the actions of haemoglobin. Br J Pharmacol 96:645–655, 1989

    • Search Google Scholar
    • Export Citation
  • 36.

    Ohta O, , Osaka K, & Siguma M, et al: Cerebral vasospasm following ruptured intracranial aneurysms, especially some contributions of potassium ion released from subarachnoid hematoma to delayed cerebral vasospasm, in Bevan JA (ed): Vascular Neuroeffector Mechanisms. New York: Raven Press, 1983, pp 353358 Ohta O, Osaka K, Siguma M, et al: Cerebral vasospasm following ruptured intracranial aneurysms, especially some contributions of potassium ion released from subarachnoid hematoma to delayed cerebral vasospasm, in Bevan JA (ed): Vascular Neuroeffector Mechanisms. New York: Raven Press, 1983, pp 353–358

    • Search Google Scholar
    • Export Citation
  • 37.

    Ohta T, , Kajikawa H, & Yoshikawa Y, et al: Cerebral vasospasm and hemoglobins: clinical and experimental studies, in Wilkins RH (ed): Cerebral Arterial Spasm. Baltimore: Williams & Wilkins, 1980, pp 166172 Ohta T, Kajikawa H, Yoshikawa Y, et al: Cerebral vasospasm and hemoglobins: clinical and experimental studies, in Wilkins RH (ed): Cerebral Arterial Spasm. Baltimore: Williams & Wilkins, 1980, pp 166–172

    • Search Google Scholar
    • Export Citation
  • 38.

    Paulson OB, & Newman EA: Does the release of potassium from astrocyte endfeet regulate cerebral blood flow? Science 237:896898, 1987 Paulson OB, Newman EA: Does the release of potassium from astrocyte endfeet regulate cerebral blood flow? Science 237:896–898, 1987

    • Search Google Scholar
    • Export Citation
  • 39.

    Pelligrino DA, , Gay RL III, & Baughman VL, et al: NO synthase inhibition modulates NMDA-induced changes in cerebral blood flow and EEG activity. Am J Physiol 271:H990H995, 1996 Pelligrino DA, Gay RL III, Baughman VL, et al: NO synthase inhibition modulates NMDA-induced changes in cerebral blood flow and EEG activity. Am J Physiol 271:H990–H995, 1996

    • Search Google Scholar
    • Export Citation
  • 40.

    Pluta RM, , Afshar JKB, & Boock RJ, et al: Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage. J Neurosurg 88:557561, 1998 Pluta RM, Afshar JKB, Boock RJ, et al: Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage. J Neurosurg 88:557–561, 1998

    • Search Google Scholar
    • Export Citation
  • 41.

    Priller J, , Haas CA, & Reddington M, et al: Calcitonin gene-related peptide and ATP induce immediate early gene expression in cultured rat microglial cells. Glia 15:447457, 1995 Priller J, Haas CA, Reddington M, et al: Calcitonin gene-related peptide and ATP induce immediate early gene expression in cultured rat microglial cells. Glia 15:447–457, 1995

    • Search Google Scholar
    • Export Citation
  • 42.

    Sarrafzadeh AS, , Unterberg AW, & Lanksch WR: Bedside-microdialysis for early detection of vasospasm after subarachnoid hemorrhage. Case report and review of the literature. Zentralbl Neurochir 59:269273, 1998 Sarrafzadeh AS, Unterberg AW, Lanksch WR: Bedside-microdialysis for early detection of vasospasm after subarachnoid hemorrhage. Case report and review of the literature. Zentralbl Neurochir 59:269–273, 1998

    • Search Google Scholar
    • Export Citation
  • 43.

    Säveland H, , Nilsson OG, & Boris-Möller F, et al: Intracerebral microdialysis of glutamate and aspartate in two vascular territories after aneurysmal subarachnoid hemorrhage. Neurosurgery 38:1220, 1996 Säveland H, Nilsson OG, Boris-Möller F, et al: Intracerebral microdialysis of glutamate and aspartate in two vascular territories after aneurysmal subarachnoid hemorrhage. Neurosurgery 38:12–20, 1996

    • Search Google Scholar
    • Export Citation
  • 44.

    Spielmeyer W, (ed): Histopathologie des Nervensystems. Berlin: Springer-Verlag, 1922 Spielmeyer W, (ed): Histopathologie des Nervensystems. Berlin: Springer-Verlag, 1922

    • Search Google Scholar
    • Export Citation
  • 45.

    Stamler JS, , Jia L, & Eu JP, et al: Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276:20342037, 1997 Stamler JS, Jia L, Eu JP, et al: Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276:2034–2037, 1997

    • Search Google Scholar
    • Export Citation
  • 46.

    Stoltenburg-Didinger G: Neuropathology of subarachnoid hemorrhage, in Bederson JB (ed): Subarachnoid Hemorrhage: Pathophysiology and Management. Park Ridge, IL: American Association of Neurological Surgeons, 1997, pp 4160 Stoltenburg-Didinger G: Neuropathology of subarachnoid hemorrhage, in Bederson JB (ed): Subarachnoid Hemorrhage: Pathophysiology and Management. Park Ridge, IL: American Association of Neurological Surgeons, 1997, pp 41–60

    • Search Google Scholar
    • Export Citation
  • 47.

    Victorov IV, & Barskov IV: A method for staining ischemic neurons in the brain and spinal cord. Pathol Physiol Exp Ther 2:53, 1993 Victorov IV, Barskov IV: A method for staining ischemic neurons in the brain and spinal cord. Pathol Physiol Exp Ther 2:53, 1993

    • Search Google Scholar
    • Export Citation
  • 48.

    White RP, , Macleod RM, & Muhlbauer MS: Evaluation of the role hemoglobin in cerebrospinal fluid plays in producing contractions of cerebral arteries. Surg Neurol 27:237242, 1987 White RP, Macleod RM, Muhlbauer MS: Evaluation of the role hemoglobin in cerebrospinal fluid plays in producing contractions of cerebral arteries. Surg Neurol 27:237–242, 1987

    • Search Google Scholar
    • Export Citation
  • 49.

    Zabramski JM: Vasospasm after subarachnoid hemorrhage, in Bederson JB (ed): Subarachnoid Hemorrhage: Pathophysiology and Management. Park Ridge, IL: American Association of Neurological Surgeons, 1997, pp 127156 Zabramski JM: Vasospasm after subarachnoid hemorrhage, in Bederson JB (ed): Subarachnoid Hemorrhage: Pathophysiology and Management. Park Ridge, IL: American Association of Neurological Surgeons, 1997, pp 127–156

    • Search Google Scholar
    • Export Citation
  • 50.

    Zhang ET, , Hansen AJ, & Wieloch T, et al: Influence of MK-801 on brain extracellular calcium and potassium activities in severe hypoglycemia. J Cereb Blood Flow Metab 10:136139, 1990 Zhang ET, Hansen AJ, Wieloch T, et al: Influence of MK-801 on brain extracellular calcium and potassium activities in severe hypoglycemia. J Cereb Blood Flow Metab 10:136–139, 1990

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 823 381 43
Full Text Views 247 19 0
PDF Downloads 141 14 0
EPUB Downloads 0 0 0