Effect of Unilateral Perinatal Hypoxic-Ischemic Brain Damage on the Gross Development of Opposite Cerebral Hemisphere

Neonatology ◽  
1994 ◽  
Vol 65 (2) ◽  
pp. 108-118 ◽  
Author(s):  
Javad Towfighi ◽  
Cathy Housman ◽  
Robert C. Vannucci ◽  
Daniel F. Heitjan
Keyword(s):  
Brain Damage ◽  
Cerebral Hemisphere ◽  
Ischemic Brain Damage ◽  
Ischemic Brain

scholarly journals Calcium Accumulation during the Evolution of Hypoxic—Ischemic Brain Damage in the Immature Rat

1988 ◽  
Vol 8 (6) ◽  
pp. 834-842 ◽  
Author(s):  
Dagmar T. Stein ◽  
Robert C. Vannucci
Keyword(s):  
Brain Damage ◽  
Cerebral Hemisphere ◽  
Ischemic Injury ◽  
Calcium Flux ◽  
Variable Degree ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Calcium Accumulation ◽  
Hypoxia Ischemia ◽  
Hypoxic Ischemic Injury

An excessive accumulation of calcium in neuronal and other tissues has been postulated to represent a “final common pathway” for cell death arising from hypoxia-ischemia. To clarify the role of altered calcium flux into and distribution within the perinatal brain undergoing hypoxic-ischemic injury, 7-day postnatal rats underwent unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in >90% of the animals. Either before or after hypoxia-ischemia, the animals received a subcutaneous injection of [45Ca]Cl2, and their brains were subjected to 45Ca autoradiography at 0–1, 5, 24, and 72 h, 7 or 15 days thereafter. During hypoxia-ischemia, calcium flux into the ipsilateral cerebral hemisphere was prominent in 13 of 14 rat pups, especially in neocortex, hippocampus, striatum, and thalamus. Calcium accumulation also occurred to a variable degree (6 of 14 animals) in the contralateral cerebral hemisphere. During recovery, radioactivity in the contralateral cerebral hemisphere was no longer apparent, whereas in the ipsilateral hemisphere, the extent of calcium accumulation was mild in four of six at 1 h, moderate in three of six at 5 h, moderate to intense in six of seven and six of seven at 24 and 72 h, respectively, and intense in three of three and two of two animals at 7 and 15 days, respectively. As during hypoxia-ischemia, the distribution of the radioactivity was most prominent in those structures that are known to be vulnerable to hypoxic-ischemic injury. Thus, hypoxia-ischemia is associated with enhanced calcium uptake into the immature brain, which does not dissipate but rather progressively accumulates for up to 15 days of recovery. The findings implicate a disruption of intracellular calcium homeostasis as a major factor in the evolution of perinatal hypoxic-ischemic brain damage.

scholarly journals Focal Cerebral Ischemia in the Cat: Pretreatment with a Competitive NMDA Receptor Antagonist, D-CPP-ene

1990 ◽  
Vol 10 (5) ◽  
pp. 668-674 ◽  
Author(s):  
Ross Bullock ◽  
David I. Graham ◽  
Min-Hsiung Chen ◽  
David Lowe ◽  
James McCulloch
Keyword(s):  
Cerebral Ischemia ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Brain Damage ◽  
Cerebral Hemisphere ◽  
Focal Cerebral Ischemia ◽  
Nmda Receptor Antagonist ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Permanent Occlusion

The effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D-( E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-CPP-ene; SDZ EAA 494) upon ischemic brain damage have been examined in anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of the middle cerebral artery (MCA) and the animals were killed 6 h later. The amount of early ischemic brain damage was assessed in coronal sections at 16 predetermined stereotaxic planes. Pretreatment with D-CPP-ene (15 mg/kg i.v. followed by continuous infusion at 0.17 mg/kg/min until death), 15 min prior to MCA occlusion, significantly reduced the volume of ischemic brain damage (from 20.6 ± 9.9% of the cerebral hemisphere in vehicle-treated cats to 7.2 ± 4.4% in drug-treated cats; p < 0.01). The competitive NMDA receptor antagonist D-CPP-ene is as effective as noncompetitive NMDA antagonists in reducing the amount of ischemic brain damage in this model of focal cerebral ischemia in a gyrencephalic species.

scholarly journals Carbohydrate and Energy Metabolism during the Evolution of Hypoxic-Ischemic Brain Damage in the Immature Rat

1990 ◽  
Vol 10 (2) ◽  
pp. 227-235 ◽  
Author(s):  
Charles Palmer ◽  
Robert M. Brucklacher ◽  
Melanie A. Christensen ◽  
Robert C. Vannucci
Keyword(s):  
Carotid Artery ◽  
Brain Damage ◽  
Cerebral Hemisphere ◽  
Tissue Injury ◽  
Adenine Nucleotides ◽  
High Energy ◽  
Cerebral Hypoxia ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Hypoxia Ischemia

The brain damage that evolves from perinatal cerebral hypoxia-ischemia may involve lingering disturbances in metabolic activity that proceed into the recovery period. To clarify this issue, we determined the carbohydrate and energy status of cerebral tissue using enzymatic, fluorometric techniques in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-day postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37°C. This insult is known to produce tissue injury (selective neuronal necrosis or infarction) predominantly in the cerebral hemisphere ipsilateral to the carotid artery occlusion in 92% of the animals. Rat pups were quick-frozen in liquid nitrogen at 0, 1, 4, 12, 24, or 72 h of recovery; littermate controls underwent neither ligation nor hypoxia. Glucose in both cerebral hemispheres was nearly completely exhausted during hypoxia-ischemia, with concurrent increases in lactate to 10 mmol/kg. During recovery, glucose promptly increased above control values, suggesting an inhibition of glycolytic flux, as documented in the ipsilateral cerebral hemisphere by measurement of glucose utilization (CMRglc) at 24 h. Tissue lactate declined rapidly during recovery but remained slightly elevated in the ipsilateral hemisphere for 12 h. Phosphocreatine (P∼Cr) and ATP in the ipsilateral cerebral hemisphere were 14 and 26% of control (p < 0.001) at the end of hypoxia-ischemia; total adenine nucleotides (ATP + ADP + AMP) also were partially depleted (–46%). During the first hour of recovery, mean P∼Cr was replenished to within 90% of baseline, whereas mean ATP was incompletely restored to 68–81% of control (p < 0.05). Individual ATP and total adenine nucleotide values were >2 SD below control levels in 17/24 (71%) brains at all intervals of recovery. Both ATP and total adenine nucleotides were inversely correlated with tissue water content, reflecting the extent of cerebral edema. No major alterations in the high-energy phosphate reserves occurred in the contralateral cerebral hemisphere either during or following hypoxia-ischemia. Thus, following perinatal cerebral hypoxia-ischemia, ATP and total adenine nucleotides never recover completely in brains undergoing damage but rather are permanently depleted to levels that reflect the severity of tissue injury. Recovery of P∼Cr to near normal levels can occur despite evolving brain damage. The findings have relevance to the assessment of asphyxiated newborn humans using magnetic resonance spectroscopy.

scholarly journals Cerebral Glucose and Energy Utilization during the Evolution of Hypoxic—Ischemic Brain Damage in the Immature Rat

1994 ◽  
Vol 14 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Robert C. Vannucci ◽  
Jermone Y. Yager ◽  
Susan J. Vannucci
Keyword(s):  
Carotid Artery ◽  
Brain Damage ◽  
Cerebral Hemisphere ◽  
Energy Utilization ◽  
Contralateral Hemisphere ◽  
Early Recovery ◽  
Ischemic Brain Damage ◽  
Ipsilateral Hemisphere ◽  
Ischemic Brain ◽  
Hypoxia Ischemia

The cerebral metabolic rate for glucose (CMRg1) and cerebral energy utilization (CEU) were assessed in immature rats during recovery from cerebral hypoxia–ischemia. CMRg1 was determined using a modification of the Sokoloff technique with 2-deoxy-[14C]glucose (2-DG) as the radioactive tracer. CEU was determined using the Lowry decapitation technique. Seven-day postnatal rats underwent unilateral common carotid artery ligation, followed 4 h thereafter by exposure to 8% oxygen at 37°C for 3 h. At 1, 4, or 24 h of recovery, the rat pups underwent those procedures necessary for the measurement of either CMRg1 or CEU. At 1 h of recovery, the CMRg1 of the cerebral hemisphere ipsilateral to the carotid artery occlusion was 97% of the control rate (8.7 μmol 100 g−1 min−1) but was only 48% of the control in the contralateral hemisphere. At 4 h of recovery, the CMRg1 was increased 49% above baseline in the ipsilateral hemisphere, decreasing thereafter to 84% of the control at 24 h. The CMRg1 of the contralateral hemisphere normalized by 4 h of recovery. An inverse correlation between endogenous concentrations of ATP or phosphocreatine and CMRg1 in the ipsilateral hemisphere was apparent at 4 h of recovery. CEU in the ipsilateral cerebral hemisphere was 64 and 46% of the control (3.47 mmol ∼P/kg/min) at 1 and 24 h, respectively (p < 0.05) and 77% of the control at 4 h of recovery. CEU in the contralateral hemisphere was unchanged from the control at all measured intervals. Correlation of the alterations in CMRg1 with those in CEU at the same intervals indicated that substrate supply exceeds energy utilization during early recovery from hypoxia-ischemia. The discrepancy combined with a persistent disruption of the cerebral energy state implies the existence of an uncoupling of mitochondrial oxidative phosphorylation as one mechanism for the occurrence of perinatal hypoxic-ischemic brain damage.

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