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      Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study Translated title: Utilização de glicose durante o estado de mal epiléptico no modelo de epilepsia induzido pela pilocarpina: um estudo qualitativo

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          Abstract

          Status epilepticus (SE) is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG) procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO) using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6%), caudate-putamen (+30.6%), frontoparietal cortex (+32.2%), amygdala (+31.7%), entorrinal cortex (+28.2%), thalamic nucleus (+93.5%), pre-tectal area (+50.1%) and substantia nigra (+50.3%) when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus.

          Translated abstract

          O estado de mal epiléptico (SE) é uma emergência médica e está associado a lesão cerebral. O procedimento da [14C] desoxiglicose tem sido utilizado para avaliar as alterações da atividade funcional cerebral induzidas por agentes farmacológicos e toxicológicos. O objetivo deste estudo foi verificar as alterações metabólicas do cérebro de ratos durante o SE induzido pela pilocarpina, para tanto, utilizamos a técnica de mapeamento funcional da [14C] desoxiglicose. Ratos machos da raça Wistar foram submetidos ao SE induzido pela pilocarpina durante período de 6 horas; 45 minutos antes de se completar 6 horas de SE, tais animais receberam uma injeção de [14C] desoxiglicose por via venosa (veia jugular). Os animais pertencentes ao grupo controle foram submetidos aos mesmos procedimentos, no entanto, receberam solução salina e não pilocarpina. As fatias cerebrais foram preparadas e expostas em filme de raioX por um período de sete dias. A análise da densidade óptica de cada região foi obtida por analisador digital de estado sólido. Tal análise revelou aumento no consumo de glicose durante o SE nas seguintes regiões: formação hipocampal (+50,6%), núcleo caudado-putamen (+30,6%), córtex frontoparietal (+32,2%), amigdala (+31,7%), córtex entorrinal (+28,2%), complexo talâmico (+93,5%), área pré-tectal (+50,1%) e substância negra (+50,3%), quando comparadas com os animais pertencentes ao grupo controle. Nossos resultados sugerem que a ativação dessas estruturas deve ser particularmente importante nos mecanismos de desencadeamento e alastramento da atividade epiléptica durante o estado de mal epiléptico.

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          Most cited references33

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          The pilocarpine model of epilepsy.

          The systemic administration of a potent muscarinic agonist pilocarpine in rats promotes sequential behavioural and electrographic changes that can be divided in three distinct periods: (a) an acute period that built up progressively into a limbic status epilepticus and that lasts 24 h, (b) a silent period with a progressive normalization of EEG and behaviour which varies from 4 to 44 days, and (c) a chronic period with spontaneous recurrent seizures (SRSs). The main features of the SRSs observed during the long-term period resemble those of human complex partial seizures and recurs 2-3 times per week per animal. Therefore, this novel and unique experimental approach may serve as a model of epilepsy mimicking the human condition.
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            The biochemical basis and pathophysiology of status epilepticus.

            E Lothman (1990)
            Status epilepticus (SE), both convulsive and nonconvulsive, can arise from diverse etiologies in either a normal brain or a previously epileptic brain. SE has a distinct natural history and unattended can lead to profound, life-threatening, systemic metabolic and physiologic disturbances. These factors may account for the poor prognosis associated with this disorder. However, there is mounting experimental evidence that SE itself, independent of metabolic and physiologic disturbances, leads to lasting brain dysfunction.
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              Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage.

              M Ingvar (1985)
              After long periods of status epilepticus, selective neuronal necrosis is incurred in the neocortex (layer III-IV), in the hippocampus (CA1 and CA4), and in the thalamus (VPL-VPM). In these areas the cerebral metabolic rate for glucose is increased to between 200-300% of control, indicating a correlation between neuronal damage and enhanced neuronal activity. Measurements of local cerebral blood flow indicate that the damage is not due to insufficient supply of oxygen. In most rats with status epilepticus lasting longer than 30 minutes, an infarction develops in the substantia nigra pars reticulata. In this region the metabolic rate is first increased but later during the seizure activity falls to very low values indicating cell necrosis. prolonged neuronal hyperactivity with a concomitant increase in the metabolic rate for glucose is a prerequisite for the development of neuronal damage. However, the necrosis of the SNPR demonstrates that other factors determine the vulnerability of neurons to hyperexcitation, e.g., the type of agonist acting on the neuron.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                anp
                Arquivos de Neuro-Psiquiatria
                Arq. Neuro-Psiquiatr.
                Academia Brasileira de Neurologia - ABNEURO (São Paulo )
                1678-4227
                June 2002
                : 60
                : 2A
                : 198-203
                Affiliations
                [1 ] Universidade de Mogi das Cruzes
                [2 ] Universidade Federal de São Paulo Brazil
                [3 ] Universidade Federal de São Paulo Brazil
                [4 ] Universidade Federal de São Paulo Brazil
                [5 ] Universidade Federal de São Paulo Brazil
                Article
                S0004-282X2002000200003
                10.1590/S0004-282X2002000200003
                8b4846b9-9dec-4a11-b0e9-d86b01894b1e

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0004-282X&lng=en
                Categories
                NEUROSCIENCES
                PSYCHIATRY

                Neurosciences,Clinical Psychology & Psychiatry
                pilocarpine,seizure,status epilepticus,desoxiglicose,pilocarpina,crises epilépticas,estado de mal epiléptico,deoxyglucose

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