METABOLIC RESPONSE TO FOCAL PENICILLIN SEIZURES IN RAT: SPIKE DISCHARGE VS. AFTERDISCHARGE 1

Abstract– The correlations among clinical events, electrocorticogram, histology, size of focus, and biochemical changes were examined in a model of focal penicillin seizures in rats. Ten units of penicillin injected into the motor cortex were found to be the threshold dose for producing repetitive spike discharges. These were associated with synchronous contralateral muscle jerks which reached a peak intensity in 10 min and fell off rapidly in 45–90 min. The half‐life of penicillin in the cortex was 15 min, with little diffusion from the site of injection. The size of the metabolic focus was determined by autoradiography with [2‐14C]deoxyglucose and was 6.5 times larger than the diffusion of penicillin. Increased glucose utilization appeared in the focus and in cortical columns in the contralateral homo‐typic cortex.

[1]  B. Siesjö,et al.  THE EFFECT OF HYPERCAPNIA UPON INTRACELLULAR pH IN THE BRAIN, EVALUATED BY THE BICARBONATE‐ CARBONIC ACID METHOD AND FROM THE CREATINE PHOSPHOKINASE EQUILIBRIUM , 1972, Journal of neurochemistry.

[2]  R. Crowell.  Distant effects of a focal epileptogenic process. , 1970, Brain research.

[3]  B. Sacktor,et al.  Regulation of glycolysis in brain, in situ, during convulsions. , 1966, The Journal of biological chemistry.

[4]  D. Prince,et al.  Effect of penicillin on an excitatory synapse , 1975, Brain Research.

[5]  F Plum,et al.  Cerebral metabolic and circulatory responses to induced convulsions in animals. , 1968, Archives of neurology.

[6]  W H Calvin,et al.  Synaptic potential summation and repetitive firing mechanisms: input-output theory for the recruitment of neurons into epileptic bursting firing patterns. , 1972, Brain research.

[7]  R. C. Collins,et al.  Metabolic anatomy of focal motor seizures. , 1976, Archives of neurology.

[8]  M. Larrabee,et al.  GLUCOSE CONSUMPTION AND LACTATE PRODUCTION IN A MAMMALIAN SYMPATHETIC GANGLION AT REST AND IN ACTIVITY * , 1958, Journal of neurochemistry.

[9]  W. Schuette,et al.  Oxidative metabolism during recurrent seizures in the penicillin treated hippocampus. , 1974, Electroencephalography and Clinical Neurophysiology.

[10]  O. H. Lowry,et al.  CHANGES IN METABOLITES OF THE ENERGY RESERVES IN INDIVIDUAL LAYERS OF MOUSE CEREBRAL CORTEX AND SUBJACENT WHITE MATTER DURING ISCHAEMIA AND ANAESTHESIA 1 , 1970, Journal of neurochemistry.

[11]  J. Passonneau,et al.  THE EFFECT OF VOLATILE ANAESTHETICS ON LEVELS OF METABOLITES AND ON METABOLIC RATE IN BRAIN 1 , 1971, Journal of neurochemistry.

[12]  B. Meldrum,et al.  Prolonged epileptic seizures in primates. Ischemic cell change and its relation to ictal physiological events. , 1973, Archives of neurology.

[13]  P. Swanson.  Penicillin-induced metabolic alterations in isolated cerebral cortex. , 1972, Archives of neurology.

[14]  O. H. Lowry,et al.  CONTROL OF GLYCOGEN LEVELS IN BRAIN 1 , 1968, Journal of neurochemistry.

[15]  G. Ayala,et al.  Penicillin as Epileptogenic Agent: Its Effect on an Isolated Neuron , 1970, Science.

[16]  O. H. Lowry,et al.  EFFECTS OF CONVULSANTS ON ENERGY RESERVES IN THE CEREBRAL CORTEX * , 1967, Journal of neurochemistry.

[17]  N. Lassen,et al.  Brain extracellular pH: the main factor controlling cerebral blood flow. , 1968, Scandinavian journal of clinical and laboratory investigation.

[18]  G F Ayala,et al.  Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. , 1970, Journal of neurophysiology.

[19]  M. Reivich,et al.  Mapping of functional neural pathways by autoradiographic survey of local metabolic rate with (14C)deoxyglucose. , 1975, Science.

[20]  M. O’Connor,et al.  Effects of potassium on oxidative metabolism and seizures. , 1973, Electroencephalography and clinical neurophysiology.

[21]  Reduced nicotinamide adenine dinucleotide and depolarization in neurons. , 1975, The American journal of physiology.

[22]  J B Ranck,et al.  Potassium accumulation in interstitial space during epileptiform seizures. , 1970, Experimental neurology.

[23]  C. A. Marsan,et al.  CORTICAL CELLULAR PHENOMENA IN EXPERIMENTAL EPILEPSY: INTERICTAL MANIFESTATIONS. , 1964, Experimental neurology.

[24]  F Plum,et al.  Brief hypoxia-ischemia initially damages cerebral neurons. , 1975, Archives of neurology.

[25]  B. Siesjö,et al.  The effect of asphyxia upon the lactate, pyruvate and bicarbonate concentrations of brain tissue and cisternal CSF, and upon the tissue concentrations of phosphocreatine and adenine nucleotides in anesthetized rats. , 1970, Acta physiologica Scandinavica.

[26]  T. Duffy,et al.  CONTROL OF THE REDOX STATE OF THE PYRIDINE NUCLEOTIDES IN THE RAT CEREBRAL CORTEX. EFFECT OF ELECTROSHOCK‐INDUCED SEIZURES , 1975, Journal of neurochemistry.

[27]  D. Prince,et al.  Extracellular potassium activity during epileptogenesis. , 1974, Experimental neurology.

[28]  E. G. Jones,et al.  Commissural and cortico-cortical "columns" in the somatic sensory cortex of primates , 1975, Science.

[29]  M. Dichter,et al.  Penicillin epilepsy in isolated islands of hippocampus. , 1973, Electroencephalography and clinical neurophysiology.

[30]  J. Ferrendelli,et al.  THE EFFECT OF AUDIOGENIC SEIZURES ON REGIONAL CNS ENERGY RESERVES, GLYCOLYSIS AND CITRIC ACID CYCLE FLUX 1 , 1971, Journal of neurochemistry.

[31]  F. Plum,et al.  Graded hypoxia-oligemia in rat brain. I. Biochemical alterations and their implications. , 1973, Archives of neurology.

[32]  F Plum,et al.  Cerebral energy metabolism, pH, and blood flow during seizures in the cat. , 1974, The American journal of physiology.

[33]  R. A. Davidoff.  Penicillin and inhibition in the cat spinal cord. , 1972, Brain research.

[34]  R. C. Collins,et al.  Cerebral energy metabolism during electroshock seizures in mice. , 1970, The American journal of physiology.

[35]  G. Sypert,et al.  Extracellular potassium concentration changes during propagated seizures in neocortex. , 1973, Experimental neurology.

[36]  J. Sung,et al.  ULTRASTRUCTURE OF PENICILLIN‐INDUCED EPILEPTOGENIC LESION OF THE CEREBRAL CORTEX IN CATS , 1971, Journal of neuropathology and experimental neurology.

[37]  G. Broggi,et al.  Fine structure of cat hippocampus during sustained seizure. , 1970, Brain research.

[38]  M. Dichter,et al.  Silent cells during interictal discharges and seizures in hippocampal penicillin foci. Evidence for the role of extracellular K+ in the transition from the interictal state to seizures. , 1972, Brain research.

[39]  D. Prince,et al.  Control mechanisms in cortical epileptogenic foci. "Surround" inhibition. , 1967, Archives of neurology.

[40]  I. Cameron,et al.  The Effect of Local Changes in Bicarbonate and Potassium Concentration on Hypothalamic Blood Flow , 1975 .

[41]  H. Mcilwain,et al.  Electrical stimulation in vitro of the metabolism of glucose by mammalian cerebral cortex. , 1951, Biochemical Journal.

[42]  R. Ratcheson,et al.  METABOLIC CHANGES IN THE BRAINS OF MICE FROZEN IN LIQUID NITROGEN , 1973, Journal of neurochemistry.

[43]  J. Ferrendelli,et al.  THE EFFECT OF ELECTROSHOCK ON REGIONAL CNS ENERGY RESERVES IN MICE 1 , 1971, Journal of neurochemistry.

[44]  O. H. Lowry,et al.  EFFECT OF ISCHEMIA ON KNOWN SUBSTRATES AND COFACTORS OF THE GLYCOLYTIC PATHWAY IN BRAIN. , 1964, The Journal of biological chemistry.

[45]  G F Ayala,et al.  Genesis of epileptic interictal spikes. New knowledge of cortical feedback systems suggests a neurophysiological explanation of brief paroxysms. , 1973, Brain research.

[46]  O. H. Lowry,et al.  CEREBRAL CARBOHYDRATE METABOLISM DURING ACUTE HYPOXIA AND RECOVERY 1 , 1972, Journal of neurochemistry.