Glutamatergic System is Affected in Brain from an Hyperthermia-Induced Seizures Rat Model.

One of the most frequent neurological disorders in children is febrile seizures (FS), a risk for epilepsy in adults. Glutamate is the main excitatory neurotransmitter in CNS acting through ionotropic and metabotropic receptors. Excess of glutamate in the extracellular space elicits excitotoxicity and has been associated with neurological disorders, such as epilepsy. The removal of extracellular glutamate by excitatory amino acid transporters (EATT) plays an important neuroprotective role. GLT-1 is the main EAAT present in the cortex brain. On the other hand, an increase in metabotropic glutamate receptors 5 (mGlu5R) levels or their overstimulation have been related to the appearance of seizure events in different animal models and in temporal lobe epilepsy in humans. In this work, the status of several components of the glutamatergic system has been analysed in the cortex brain from an FS rat model at short (48 h) and long (20 days) term after hyperthermia-induced seizures. At the short term, we detected increased GLT-1 levels, reduced glutamate concentration, and unchanged mGlu5R levels, without neuronal loss. However, at the long term, an increase in mGlu5R levels together with a decrease in both GLT-1 and glutamate levels were observed. These changes were associated with the appearance of an anxious phenotype. These results suggest a neuroprotective role of the glutamatergic components mGlu5R and GLT-1 at the short term. However, this neuroprotective effect seems to be lost at the long term, leading to an anxious phenotype and suggesting an increased vulnerability and propensity to epileptic events in adults.

Hyperthermia-induced seizures during neonatal period alter the functionality of A1 and A2A receptors in the cerebellum and evoke fine motor impairment and gait disturbances in adult rats.

Febrile seizures (FS) are one of the most common types of convulsive disorder of early childhood and they can be classified into simple and prolonged depending on the duration. Nowadays, simple FS have a good prognosis but there is controversy about the outcome of prolonged FS. In a previous work using an animal model of prolonged FS, we showed that hiperthermia-induced seizures (HIS) evoked fine motor coordination impairment and gait disturbances in adolescent rats in a process in which seemed to be involved modulation of the cerebellar adenosinergic system. The aim of the present work was to verify whether the effect was maintained in adulthood. To this end, neonatal rats (PD 12) were exposed to HIS and after 48 days (PD 60) they were assayed on balance beam and footprint tests. Animals were sacrificed 53 days after HIS and adenosine A1 and A2A receptor signalling pathways were studied in cerebellar plasma membranes by using radioligand binding assays and by measuring the activities of 5´-nucleotidase and adenylyl cyclase. Results obtained revealed that adult rats exposed to HIS showed gait disturbances and motor impairments. Besides, animals exposed to hyperthermic insult showed an increase in adenosine A2A receptor functionality and 5´-nucleotidase activity. Surprisingly, the functionality of the adenosine A1 receptor resulted significantly changed causing stimulation instead of inhibition of adenylate cyclase activity. These results showed that the effect of prolonged FS at the early age also persist in adulthood suggesting on must pay attention to FS in children.