RESUMO
Granule cells of the dentate gyrus can express neuropeptide-Y (NPY) in several models of epilepsy involving limbic seizures, however, the nature of this ectopic expression is not well understood at present. We have studied the expression of NPY-immunoreactivity in mossy fibres contralateral to a unilateral intrahippocampal injection of kainic acid and report that ectopic mossy fibre NPY-immunoreactivity is observed throughout the contralateral hippocampus.
Assuntos
Agonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/química , Ácido Caínico/farmacologia , Neuropeptídeo Y/imunologia , Animais , Especificidade de Anticorpos , Epilepsia/fisiopatologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Microinjeções , Neuropeptídeo Y/análise , Ratos , Ratos WistarRESUMO
We have previously reported an ectopic expression of neuropeptide-Y (NPY) immunoreactivity in mossy fibres (MFs) in the contralateral hippocampus following a unilateral intrahippocampal (IH) injection of kainic acid (KA). In the present study we report that, in addition to MF NPY expression, unilateral IH KA injections also induce tolerance towards a subsequent intracerebroventricular (ICV) contralateral KA injection, resulting in a reduction in the number of overt seizures and degree of cell loss.
Assuntos
Tolerância a Medicamentos , Hipocampo/metabolismo , Ácido Caínico/farmacologia , Fibras Nervosas/metabolismo , Neuropeptídeo Y/metabolismo , Animais , Hipocampo/efeitos dos fármacos , Masculino , Neuropeptídeo Y/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Granule cell dispersion (GCD) into the dentate gyrus (DG) molecular layer was observed in hippocampal specimens in 10 out of 22 cases of human non-lesional temporal lobe epilepsy (TLE) and was associated with hippocampal sclerosis (HS). The presence of GCD was significantly linked to events of epileptic nature arising during the first 4 years of life but not with the durations of epilepsy, nor the number of seizures. Dispersion could be induced by seizure-linked structural plasticity occurring during a specific early permissive period.
Assuntos
Giro Denteado/patologia , Esclerose Cerebral Difusa de Schilder/patologia , Epilepsia do Lobo Temporal/patologia , Neurônios/patologia , Morte Celular , Criança , Humanos , Estatísticas não Paramétricas , Fatores de TempoRESUMO
The stratum granulosum (SG) of the fascia dentata from 17 human epileptic hippocampi was assessed in terms of width, volumetric cell density (VCD) and percentage of cell loss to study the granule cell dispersion (GCD) phenomenon described by Houser. GCD was considered when three conditions were observed, the SG was wider than 120 microns, granule cell (GC) somata did not remain in close apposition to one another the normal clear boundary between the molecular layer and the SG was not maintained. GCD involved a partial zone of the SG in six cases and the whole SG in two cases. Dynorphin mRNA in-situ hybridization was performed in two cases and allowed us to affirm that dispersed cells are actually GC. A close correlation linked GCD, GC loss and VCD decrease in diffuse CA4, laminated CA4, CA3, CA2 and CA1. The discussion is focused on the possible causes of dispersion. Some arguments did not suggest for a migration arrest during development. Nevertheless, in one case, a cluster of horizontal cells in the inner part of the molecular layer could evoke the persistence of normally transient cells during ontogenesis. A neo-migration due to permissive phenomenon induced by gliogenesis, mossy fibers sprouting in the supra-granular layer and over-expression of growth factors is suggested from experimental data. Nevertheless a straining due to the tissue shrinkage observed in severe hippocampal sclerosis (HS) could also be involved in the origin of GCD.
Assuntos
Morte Celular/fisiologia , Giro Denteado/patologia , Epilepsia do Lobo Temporal/patologia , Adolescente , Adulto , Idade de Início , Contagem de Células , Criança , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Hibridização In Situ , MasculinoRESUMO
7 cases of pure multiple subpial transection (MST) without associated cortical resection, for treatment of pharmaco-resistant partial epilepsy localized in highly functional cortical area, are reported. The transections were performed following the technique described by Morrell. The follow-up period ranged from 1 to 4 years. MST induced no significant neurological handicap: only 2 patients experiencing a transitory sensory-motor deficit and with total recovery within 1 month. With respect to seizures, 5 patients were improved with a decrease in seizure frequency of 100, 95, 75, 60 and 40%, respectively. Complex partial seizures changed postoperatively into simple partial seizures in 1 case. In conclusion, this procedure seems to be adequate, although no statistically significant results are available at this time. In our series, we believe failures could be attributed to either a very restricted area of transection or to an incorrect delimitation of the epileptic focus.
Assuntos
Epilepsias Parciais/cirurgia , Pia-Máter/cirurgia , Adulto , Criança , Resistência a Medicamentos , Eletroencefalografia , Feminino , Seguimentos , Humanos , MasculinoRESUMO
OBJECT: The goal of this study was to determine whether regional cerebral blood flow (rCBF) changes that were found contralaterally to a verified unilateral epileptic focus were associated with the spatiotemporal organization of epileptic abnormalities. METHODS: The CBF in both hippocampi was assessed using stable Xe-enhanced computerized tomography in a series of 19 patients with unilateral mesiotemporal epilepsy. Results were compared according to the distribution of interictal spiking and the spatiotemporal organization of the ictal discharges as determined by stereoelectroencephalography. Two groups were defined: in Group 1 (nine patients), the discharge remained unilateral; in Group 2 (10 patients), the discharge spread to contralateral mesiotemporal structures. For Group 1, the rates of ipsi- and contralateral hippocampal blood flow (HBF) were 32.88+/-15.53 and 45.88+/-17.19 ml/100 g/minute, respectively, whereas in Group 2 they were 36.7+/-11.54 and 36.4+/-11.27 ml/100 g/minute (mean+/-standard deviation). A two-way analysis of variance combining type of seizure (Group 1 compared with Group 2) and HBF (ipsi- compared with contralateral absolute values) demonstrated a main effect for HBF (F[1,17] = 5.051; p = 0.0382), a significant interaction between the two factors (F[1,17] = 6.188; p = 0.0235), and no main effect for type of seizure (F[1,17] = 0.258; p = 0.6178). CONCLUSIONS: In unilateral mesiotemporal epilepsy, asymmetrical interictal hippocampal perfusion was correlated with restricted unilateral ictal discharges, whereas bilateral hippocampal hypoperfusion was correlated with ictal discharges spreading to the contralateral mesiotemporal structures. The lack of correlation between the degree of hypoperfusion and the percentage of neuron cell loss indicated that the decrease in rCBF has both functional and lesional origins.
Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Hipocampo/irrigação sanguínea , Adolescente , Adulto , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico , Hipocampo/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Fluxo Sanguíneo Regional/fisiologia , Técnicas Estereotáxicas , Tecnécio Tc 99m Exametazima , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , XenônioRESUMO
BACKGROUND AND PURPOSE: Changes occurring in neuropeptide-Y immunoreactivity after kainic acid injection in rats and their possible consequences on seizure-brain damage were studied. METHODS: First, an intra-hippocampal kainic acid injection was performed (n = 7), inducing an ectopic and bilateral neuropeptide-Y immunoreactivity in mossy fibers. On the side of the injection, this neuropeptide-Y staining was associated with dramatic neuronal loss whereas, in the contralateral hippocampus staining was observed without associated neuronal loss. The CA3 a-b pyramidal cell loss induced by an intra-ventricular kainic acid injection was then compared between a control group (n = 6) and a pre-conditioned group (n = 6) characterized by neuropeptide-Y staining in the mossy fibers obtained by a previous contralateral intra-hippocampal kainic acid injection as described. RESULTS: In the pre-conditioned group, the CA3 a-b pyramidal cell loss was significantly lower (m = 33.5%) than in the control group (m = 86.6%). The neuropeptide-Y inhibiting the pre-synaptic release of glutamate, glutamate-related epileptic-brain damage could be reduced when neuropeptide-Y is expressed by granulated cells. IN CONCLUSION: Seizure-linked plasticity could induce a self-protection phenomenon against excitotoxic lesions possibly partially mediated by de novo neuropeptide-Y mossy fiber expression.
Assuntos
Epilepsia/induzido quimicamente , Epilepsia/prevenção & controle , Hipocampo/metabolismo , Ácido Caínico , Neuropeptídeo Y/metabolismo , Animais , Contagem de Células/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Imuno-Histoquímica , Fibras Musgosas Hipocampais/efeitos dos fármacos , Fibras Musgosas Hipocampais/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Neuropeptídeo Y/fisiologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Ratos , Ratos WistarRESUMO
Neuropeptide-Y (NPY) is expressed by granule cells and mossy fibres of the hippocampal dentate gyrus during experimental temporal lobe epilepsy (TLE). This expression may represent an endogenous damping mechanism since NPY has been shown to block seizure-like events following high-frequency stimulation in hippocampal slices. The pilocarpine (PILO) model of epilepsy is characterized by an acute period of status epilepticus followed by spontaneous recurrent seizures and related brain damage. We report peroxidase-antiperoxidase immunostaining for NPY in several brain regions in this model. PILO-injected animals exhibited NPY immunoreactivity in the region of the mossy fibre terminals, in the dentate gyrus inner molecular layer and, in a few cases, within presumed granule cells. NPY immunoreactivity was also dramatically changed in the entorhinal cortex, amygdala and sensorimotor areas. In addition, PILO injected animals exhibited a reduction in the number of NPY-immunoreactive interneurons compared with controls. The results demonstrate that changes in NPY expression, including expression in the granule cells and mossy fibres and the loss of vulnerable NPY neurons, are present in the PILO model of TLE. However, the significance of this changed synthesis of NPY remains to be determined.
Assuntos
Encéfalo/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Neuropeptídeo Y/metabolismo , Animais , Encéfalo/anatomia & histologia , Encéfalo/patologia , Contagem de Células , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/patologia , Imuno-Histoquímica , Interneurônios/metabolismo , Interneurônios/patologia , Masculino , Agonistas Muscarínicos/toxicidade , Pilocarpina/toxicidade , Ratos , Ratos WistarRESUMO
PURPOSE: Correlations between granule cell dispersion (GCD), collateral mossy fiber (MF) sprouting, and hippocampal cell loss were studied to assess the relation between GCD and synaptic reorganization in the dentate gyrus of patients with epilepsy. METHODS: Twenty specimens from patients with medically intractable temporal lobe epilepsy (TLE) were studied along with two control specimens. GCD was considered to be present when the stratum granulosum was wider than 120 microm, the close apposition between the granule cell (GC) soma was lost, and GCs were scattered in the molecular layer (ML). Patterns of MF sprouting were differentiated as wide or narrow according to the area of neo-Timm's staining in the ML. GC loss and volumetric cell-density decreases in the different subfields were assessed. RESULTS: MF sprouting was observed in 16 (80%) and GCD in nine (45%) cases. A significant correlation was found between MF sprouting and cell loss in all the subfields except the cornu Ammonis field 2 (CA2). A wide band of MF sprouting was associated with severe cell loss. Cases with GCD had a wide band of MF sprouting and also a higher degree of cell loss than cases without GCD. CONCLUSION: GCD is associated with a specific pattern of MF sprouting, but cell loss was found to be a major determinant for MF reorganization.