A single episode of neonatal seizures alters the cerebellum of immature rats.

Department of Animal Biology, Laboratory of Cell Biology and Neurobiology, University of Pavia, via Ferrata 1, 27100 Pavia, Italy.
Epilepsy research (Impact Factor: 2.48). 01/2011; 93(1):17-24. DOI: 10.1016/j.eplepsyres.2010.10.013
Source: PubMed

ABSTRACT to test whether a single episode of early-life seizures may interfere with the development of the cerebellum. The cerebellum is particularly vulnerable in infants, since it is characterized by an important postnatal histogenesis that leads to the settling of adult circuitry.
seizures were induced in 10-day-old Wistar rats with a single convulsive dose (80μg/g b.w., s.c.) of pentylentetrazole (PTZ). Immediately after rats were treated with (3)H-thymidine ((3)HTdR, 2.5μCi/g b.w, s.c.). Rats were killed 4h later and paraffin sections of the cerebellar vermis were processed for (3)HTdR autoradiography and immunocytochemistry for 2/3 subunits of AMPA glutamate receptor (GluR2/3), glutamate transporter 1 (GLT1) and calbindin.
seizures reduced the proliferation rate of cells in the external germinal layer. Purkinje cells showed increased GluR2/3 immunoreactivity. However, some Purkinje cells were unstained or lost. Increased GLT1 immunoreactivity was present in glial cells surrounding Purkinje cells. Calbindin immunoreaction confirmed that some Purkinje cells were missed. The remaining Purkinje cells showed large spheroids along the course of their axon.
data indicate that seizures lead to a loss and alteration of Purkinje cells in the cerebellum of immature rats. Since at 10 days of life Purkinje cells are no more proliferating, the loss of Purkinje cells should be permanent.

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    ABSTRACT: Incidence of status epilepticus (SE) is higher in children than in adults and SE can be induced in developing rats. The cerebellum can be affected after SE; however, consequences of cerebellar amino acid transmission have been poorly studied. The goal of this study was to determine amino acid tissue concentration and GABA(A) receptor binding in the immature rat cerebellum after an episode of SE. Thirteen-day-old (P13) rat pups received intraperitoneal injections of lithium chloride (3 mEq/kg). Twenty hours later, on P14, SE was induced by subcutaneous injection of pilocarpine hydrochloride (60 mg/kg). Control animals were given an equal volume of saline subcutaneously. Animals were killed 24h after SE induction, the cerebellum was quickly removed, and the vermis and hemispheres were rapidly dissected out on ice. Amino acid tissue concentrations in the vermis and hemispheres were evaluated by HPLC and fluorescent detection. GABA(A) receptor binding in the medial vermis was analyzed by in vitro autoradiography. SE increased the tissue levels of the inhibitory amino acids taurine (80%) and alanine (91%), as well as glutamine (168%) in the cerebellar hemisphere; no changes were observed in the vermis. SE did not modify GABA(A) receptor binding in any cerebellar lobule from the vermis. Our data demonstrate that SE produces region-specific changes in amino acid concentrations in the developing cerebellum.
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