glycogen and Brain-Injuries

The present study has examined the anticonvulsant and neuroprotective effect of group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the model of seizures induced in immature 12-day-old rats by bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-tonic seizures, approximately 45-50 min after infusion. Comparable time intervals were used for sacrificing the pups which had received 2R,4R-APDC. Low doses of 2R,4R-APDC (0.05 nmol/side) provided a pronounced anticonvulsant effect which was abolished by pretreatment with a selective group II mGluR antagonist LY341495. Generalized clonic-tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these seizures were either normalized (decrease of glucose and glycogen) or markedly reduced (an accumulation of lactate). EEG recordings support the marked anticonvulsant effect of 2R,4R-APDC, nevertheless, this was only partial. In spite of the absence of obvious motor phenomena, isolated spikes or even short periods of partial ictal activity could be observed. Isolated spikes could also be seen in some animals after application of 2R,4R-APDC alone, reflecting most likely subclinical proconvulsant activity of this agonist. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration, as revealed by Fluoro-Jade B staining, was observed in a number of brain regions following infusion of DL-HCA alone (seizure group), whereas 2R,4R-APDC pretreatment provided substantial neuroprotection. The present findings support the possibility that group II mGluRs are a promising target for a novel approach to treating epilepsy.

Topics: Amino Acids; Animals; Animals, Newborn; Anticonvulsants; Behavior, Animal; Brain; Brain Chemistry; Brain Injuries; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Excitatory Amino Acid Antagonists; Fluoresceins; Fluorescent Dyes; Functional Laterality; Glucose; Glycogen; Homocysteine; Lactic Acid; Male; Nerve Degeneration; Organic Chemicals; Proline; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate; Seizures; Time Factors; Xanthenes

Previous studies have demonstrated that traumatic brain injury (TBI) increases the vulnerability of the brain to an acute episode of hypoxia-ischemia. The objective of the present study was to determine whether TBI alters the vulnerability of the brain to a delayed episode of ischemia and, if so, to identify contributing mechanisms. Sprague-Dawley rats were subjected to lateral fluid-percussion (FP) brain injury (n = 14) of moderate severity (2.3-2.5 atm), or sham-injury (n = 12). After recovery for 24 h, all animals underwent an 8-min episode of forebrain ischemia, followed by survival for 6 days. Ischemic damage in the hippocampus and cerebral cortex of the FP-injured hemisphere was compared to that in the contralateral hemisphere and to that in sham-injured animals. Remarkably, the number of surviving CA(1) neurons in the middle and lateral segments of the hippocampus in the FP-injured hemisphere was significantly greater than that in the contralateral hemisphere and sham-injured animals (p < 0.05). Likewise, in the cerebral cortex the number of damaged neurons tended to be lower in the FP-injured hemisphere than in the contralateral hemisphere. These results suggest that TBI decreased the vulnerability of the brain to a delayed episode of ischemia. To determine whether TBI triggers protective metabolic alterations, glycogen levels were measured in cerebral cortex and hippocampus in additional animals 24 h after FP-injury (n = 13) or sham-injury (n = 7). Cortical glycogen levels in the ipsilateral hemisphere increased to 12.9 +/- 6.4 mmol/kg (mean +/- SD), compared to 6.4 +/- 1.8 mmol/kg in the opposite hemisphere and 5.7 +/- 1.3 mmol/kg in sham-injured animals (p < 0.001). Similarly, in the hippocampus glycogen levels in the FP-injured hemisphere increased to 13.4 +/- 4.9 mmol/kg, compared to 8.1 +/- 2.4 mmol/kg in the contralateral hemisphere (p < 0.004) and 6.2 +/- 1.5 mmol/kg in sham-injured animals (p < 0.001). These results demonstrate that TBI triggers a marked accumulation of glycogen that may protect the brain during ischemia by serving as an endogenous source of metabolic energy.

Topics: Animals; Brain Injuries; Brain Ischemia; Cerebral Cortex; Glucose; Glycogen; Hippocampus; Male; Rats; Rats, Sprague-Dawley; Time Factors

The anaerobic mobilization of astrocyte glycogen in anoxic-ischemic regions of the oedematous human cerebral cortex is analysed.. Seventeen cortical biopsies of patients with brain trauma, brain tumours and congenital malformations were examined by conventional transmission electron microscopy.. Glycogen-rich and glycogen-depleted, clear or dense astrocytes cell bodies were observed in anoxic ischaemic regions of different brain cortical areas in perineuronal, neuropilar and perivascular localization. Glycogen-rich astrocytes showed clear or moderately dense cytoplasm and accumulation of both beta-type or monogranular glycogen granules and alpha-type or multigranular glycogen particles. Focal regions of translucent cytoplasm were observed in areas of glycogen degradation. Glycogen-depleted astrocytes exhibited a clear cytoplasm and scarce amount or absence of beta-type glycogen granules. Coexisting glycogen-rich and glycogen-depleted neuropilar astrocytic processes were observed in the vicinity of degenerated myelinated axons and degenerated axodendritic contacts. Glycogen-rich and glycogen-depleted perivascular astrocytic processes were also found surrounding injured and collapsed cerebral capillaries.. The findings suggest astrocytic glycogen mobilization during anoxic and ischaemic conditions, revealing the important contribution of astrocytes on neuronal survival under conditions of energy substrate limitations.

Topics: Adolescent; Adult; Astrocytes; Biopsy; Brain; Brain Edema; Brain Injuries; Brain Neoplasms; Cerebral Cortex; Child; Female; Glycogen; Humans; Infant; Infant, Newborn; Male; Microscopy, Electron; Middle Aged

The authors previously demonstrated, in a large-animal intracerebral hemorrhage (ICH) model, that markedly edematous ("translucent") white matter regions (> 10% increases in water contents) containing high levels of clot-derived plasma proteins rapidly develop adjacent to hematomas. The goal of the present study was to determine the concentrations of high-energy phosphate, carbohydrate substrate, and lactate in these and other perihematomal white and gray matter regions during the early hours following experimental ICH.. The authors infused autologous blood (1.7 ml) into frontal lobe white matter in a physiologically controlled model in pigs (weighing approximately 7 kg each) and froze their brains in situ at 1, 3, 5, or 8 hours postinfusion. Adenosine triphosphate (ATP), phosphocreatine (PCr), glycogen, glucose, lactate, and water contents were then measured in white and gray matter located ipsi- and contralateral to the hematomas, and metabolite concentrations in edematous brain regions were corrected for dilution. In markedly edematous white matter, glycogen and glucose concentrations increased two- to fivefold compared with control during 8 hours postinfusion. Similarly, PCr levels increased several-fold by 5 hours, whereas, except for a moderate decrease at 1 hour, ATP remained unchanged. Lactate was markedly increased (approximately 20 micromol/g) at all times. In gyral gray matter overlying the hematoma, water contents and glycogen levels were significantly increased at 5 and 8 hours, whereas lactate levels were increased two- to fourfold at all times.. These results, which demonstrate normal to increased high-energy phosphate and carbohydrate substrate concentrations in edematous perihematomal regions during the early hours following ICH, are qualitatively similar to findings in other brain injury models in which a reduction in metabolic rate develops. Because an energy deficit is not present, lactate accumulation in edematous white matter is not caused by stimulated anaerobic glycolysis. Instead, because glutamate concentrations in the blood entering the brain's extracellular space during ICH are several-fold higher than normal levels, the authors speculate, on the basis of work reported by Pellerin and Magistretti, that glutamate uptake by astrocytes leads to enhanced aerobic glycolysis and lactate is generated at a rate that exceeds utilization.

Topics: Adenosine Triphosphate; Aerobiosis; Animals; Astrocytes; Blood Proteins; Body Water; Brain Edema; Brain Injuries; Cerebral Hemorrhage; Disease Models, Animal; Energy Metabolism; Extracellular Space; Frontal Lobe; Glucose; Glutamates; Glycogen; Glycolysis; Hematoma; Lactates; Phosphocreatine; Swine; Time Factors

A Remington humane stunner was used to deliver a blow to the left side of the surgically-exposed skull in ketamine-anesthetized cats. At 15 minutes after the trauma, brain tissue was frozen in situ. In animals without visible tissue hemorrhage (Grade 0) and in those with unilateral cerebral contusions involving the cerebral cortex and white matter (Grade 2), regional cerebral metabolite concentrations were measured by enzymatic-fluorometric techniques and edema was tested with an organic gradient. No substantial changes in cerebral metabolite concentrations were observed in head-injured animals without cerebral contusions. In animals with unilateral contusions, the white matter neighboring the tissue hemorrhage had an increase in lactic acid and a decrease in phosphocreatine as compared to values from corresponding areas on the contralateral side, and in control and Grade 0 animals. The cerebral cortex adjacent to tissue hemorrhage had a variable response that ranged from metabolite concentrations within normal ranges to marked decreases in high-energy phosphates and increases in lactic acid. Metabolites of the cortex and white matter contralateral as well as distant to contusion were not statistically different from values of control animals. Changes in several metabolites correlated well with the magnitude of edema. It is concluded that focal metabolic alterations can occur shortly after severe blunt head injury, and that these events may contribute to acute traumatic cerebral edema.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Brain Edema; Brain Injuries; Cats; Glucose; Glycogen; Lactates; Phosphocreatine; Wounds, Nonpenetrating

Transection of the thoracic spinal cord in adult rats produces an astroglial reaction at the lesion site which spreads gradually to lumbar segments. We compared the spread of gliosis in cordotomized adult and neonatal rats in order to evaluate whether or not maturity of long spinal tracts is a precondition for the genesis of this histopathological reaction. By this experiment, we sought to determine whether spread of gliosis is induced by degeneration of nerve fibers in ascending and descending pathways or results from some more general reaction to injury. The spinal cords of 40 neonatal and 30 young adult rats were transected at T5, and 4 to 60 days later the cervical, thoracic, and lumbar segments were examined immunocytochemically for glial fibrillary acidic protein. In the neonatal rats, there was a moderate gliosis at the lesion site by 7 days; this reaction intensified somewhat during the next 60 days but always remained confined to the site of injury. In contrast, the lesion site of adult rats showed a much more intense gliosis; in those animals the response was maximal by 14 days and was characterized by a gradient of decreasing glial reactivity both rostrally and caudally from the transection site. These results support the hypothesis that the spread of gliosis from spinal lesions results from degeneration of the long ascending and descending fiber tracts.

Topics: Animals; Animals, Newborn; Astrocytes; Behavior, Animal; Brain Chemistry; Brain Injuries; Female; Glycogen; Histocytochemistry; Immunologic Techniques; Rats; Rats, Inbred Strains; Spinal Cord Injuries

Topics: Adaptation, Physiological; Birth Injuries; Brain Injuries; Glycogen; Humans; Infant, Newborn

Topics: 1,4-alpha-Glucan Branching Enzyme; Adenine Nucleotides; Adrenal Cortex Hormones; Animals; Blood Glucose; Body Temperature Regulation; Brain; Brain Diseases; Brain Injuries; Catecholamines; Central Nervous System; Chemical Phenomena; Chemistry, Physical; Glycogen; Glycogen Synthase; Histocytochemistry; Histological Techniques; Humans; Hypoxia, Brain; Insulin; Ischemia; Nerve Degeneration; Phenobarbital; Phosphorylases; Radiation Effects; Radiation, Ionizing; Rats; Retina

A major concern in the use of neural prostheses is whether electrical stimualtion can cause irreversible damage to neurons. The Neural Damage Model was devised to study the problem and to provide guidlines. The cerebral cortex of cats was stimulated continuously for 36 hours with balanced, biphasic waveforms. The charge per phase, charge density and current density were varied in 16 separate tests. Of these stimulus parameters the charge per phase was more closely correlatable with neuronal damage than charge density and current density. Furthermore, the findings in this study suggest that current flow is more important than electrochemical reactions in causing neural damage. Correlation between blood-brain barrier (BBB) breakdown and neuronal damage was valid only in the group of animals sacrificed immediately following stimulation. The BBB is restored within one month following electrical injury. Convulsive seizures occurred in all but one of the animals during electrical stimulation. A technique for localizing the electrode sites at autopsy and in the microscopic sections is described.

Topics: Animals; Astrocytes; Blood-Brain Barrier; Brain Injuries; Cats; Cerebral Cortex; Disease Models, Animal; Electric Stimulation; Glycogen; Neurons; Seizures

Topics: Age Factors; Animals; Brain; Brain Injuries; Cerebral Cortex; Female; Glycogen; Male; Microscopy, Electron; Rats; Succinate Dehydrogenase

Topics: Animals; Brain Edema; Brain Injuries; Cerebral Cortex; Cold Temperature; Endoplasmic Reticulum; Extracellular Space; Female; Glycogen; Inclusion Bodies; Male; Microscopy, Electron; Mitochondria; Necrosis; Neuroglia; Rats; Ribosomes

Topics: Animals; Brain Chemistry; Brain Injuries; Cerebellum; Cerebral Cortex; Glycogen; Neuroglia; Rats; Staining and Labeling

Topics: Animals; Brain Chemistry; Brain Injuries; Capillaries; Female; Glycogen; Histocytochemistry; Histological Techniques; Methods; Mice; Microchemistry; Neuroglia; Rats

Topics: Animals; Brain; Brain Injuries; Carbon Dioxide; Choline; Cytochromes; Glycogen; Histocytochemistry; Male; Nucleotides; Prednisolone; Rats

Topics: Animals; Brain Injuries; Cerebral Cortex; Cricetinae; Cytoplasm; Glucose; Glycogen; Histocytochemistry; L-Lactate Dehydrogenase; Lactates; Microscopy, Electron; Neuroglia; Nitrogen; Proteins; Rats

Topics: Brain; Brain Injuries; Enzymes; Glycogen; Hemorrhage; Humans