HGF y GCSF en epilepsia experimental

INICIO / LIVANT Europa / Epilepsia, Esquizofrenia y Trastorno Bipolar / Hgf y gcsf en epilepsia experimental

Autor: Edelfo

The Hepatocyte Growth Factor (HGF) Reduce The Convulsive Effect of Kainic Acid in Wistar Rats

Aguilar L. C1., and Islas A2.

1Instituto de Investigaciones en Neuroplasticidad y Desarrollo Celular (IINEDEC). Guadalajara, Jalisco, MEXICO.

2 Departamento de Biología Celular y Molecular. Universidad de Guadalajara, MEXICO.

The HGF has demonstrated neurotrophic activity in GABAergic neurons,increasing their survival, neuritegenesis, synaptic modulation and migration (W. Sun et al . Molecular Brain Research 103. 2002: 36– 48). HGF has also neuroprotective action against excitotoxicity in CNS neurons ( M. Ahamed Hossain et al. J. of Neurochemistry, 81. 2002: 365–378) On the other hand several evidences indicate a reduction in GABAergic activity in Epilepsy (G.L. Westbrook, ch 46: Seizures and Epilepsy. In E. Kandel. Principles Of Neural Science. McGrow Hill Ed. 2000). We tested the HGF/Scatter Factor effect in an epilepsy rat Wistar model of Kainic Acid at dosages of 10 mg / Kg via i.p., . The animals were males, 4 weeks old, 100 g of weight.The experimental group (n=10) received a pretreatment of 8 µg of HGF / Kg twice a day by subcutaneous route during seven days previous to the Kainic Acid injection. The control group received vehicle as a placebo twice a day, during seven days. Seizure severity was scored according to Racine ( R.J., Racine. Electroencephalogr. Clin. Neurophys. 32. 1972. 281– 294.) (1) Immobility, eye closure, ear twitching, twitching of vibrissae, sniffing, facial clonus; (2) head nodding associated with more severe facial clonus; (3) clonus of one forelimb; (3.5) bilateral clonus without rearing; (4) bilateral clonus accompanied by rearing; (4.5) generalized clonic seizures without rearing and falling (e.g. because of direct loss of balance); (5) rearing and falling accompanied by generalized clonic seizures.

LA SEVERIDAD CONVULSIVA SE REGISTRO DE ACUERDO A RACINE (1972)
1.- Inmovilidad, cierre ocular, jaloneos cortos y rápidos de orejas, jaloneos cortos y rápidos de folículos pilosos alrededor de la boca,respiraciones bruscas por nariz en inhalaciones cortas y audibles, clonus facial.
2.- Clonus facial mas severo asociado a inclinaciones rápidas de la cabeza.
3.- Clonus de un miembro anterior.
3.5.- Clonus bilateral de los miembros anteriores sin pararse en patas traseras.
4.- Bilateral clonus acompañado con pararse en patas traseras (levantamientos).
4.5.- Convulsiones clonicas generalizadas sin pararse y teniendo caidas.
5.- Convulsiones clonicas generalizadas acompañadas de levantamientos y caídas.
Hyperactivity in around 50% of rats that showed excess in mobility was analyzed measuring the path length in centimeters / per minute at 30, 60 and 120 minutes after Kainic Acid injection.The results in the pretreated group with HGF showed the Racine level scale mean of 1+/- 0.25 at 30 min, 1.25 +/- 0.5 at 60 min and 1.25 +/- O.5 at 120 min. Meanwhile the non pretreated group showed 2 +/- 0.5, 3.5 +/- 0.75, and 4.5 +/- 1.25 respectively. The path length mean in treated group was 25 +/- 15 cm at 30 min, 32 +/- 13 cm at 60 min and 35cm +/- 12 at 120 min. Nevertheless the non treated group showed 150 +/- 30 cm at 30 min, 460 +/- 60 cm at 60 min and 800 +/-78 cm at 120 min.75 % of rats of the non treated group died before 180 min. Meanwhile there were no deaths in the treated group.These results suggest that HGF increase the inhibitory capacity of GABAergic neurons reducing the excitatory effect of Kainic acid, improving survival and reducing seizure activity. HGF Effect On Convulsive Activity In Kainic Acid Rat Model.

HGF Diminish Hyperactivity Behavior in Rats Treated With Kainic Acid.

Percet of Survival in HGF Pretreated Rats After 3 Hours In the Kainic Acid Model.

HEPATOCYTE GROWTH FACTOR (HGF) DECREASES THE ABSOLUTE POWER IN COBALT TREATED RATS

L. C. AGUILAR1, A. MORALES-VILLAGRAN2. B. MUÑOZ1, L. MEDINA-CEJA2, L.C. AGUILAR-VENEGAS1.

1 Instituto de Investigaciones en Neuroplasticidad y Desarrollo Celular
2 CUCBA, Universidad de Guadalajara, México.

A significant decrease in seizure activity and an improvement in the abnormal coherence analysis were observed after HGF administration in rats treated with cobalt powder. In rats treated with kainic acid, the HGF showed an improvement insurvival. In another study, the HGF had neurotrophic activity on gabaergic neurons. An analysis of absolute power of EEG activity was performed in this study on cobalt treated rats under the effect of HGF.

METHODOLOGY.

Adult male Wistar rats were used for cortical electrodes implantation and cobalt powder administration, an epileptiform activity was registered using synamp amplifiers and Neuroscan 4.3 software, the acquisition rate was at 2000,1000 and 500/sec. and the frequency analysis was performed between 0.5 and 125 HZ with notch filter in 60 Hz. The first evaluation was performed twenty four hours after surgery, two EEG recordings were taken before drug. administration with a 30 minutes difference between them. After the second recording, a dosage of 4 µg/kg of HGF or sodium saline solution was administered i.p. Four additional EEG recordings were taken at 0.5, 2, 15 and 60 hours after drug and saline administration and the analysis of the absolute power was quantified. Another group was analyzed 5 days after the cobalt administration and an EEG without stimulation and an EEG during flash stimulation were obtained in similar acquisition digital rates (2000,1000 and 500 Hz).In the flash EEG it was analyzed the event related band power in a band frequency between 0.5 to 52 Hz, in the segment between 0 to 500 ms after the flash stimulation, the power was quantified, totalized, averaged and compared in experimental and control groups through a t-test, before and after HGF treatment 2 hrs, 1, 3 and 7 days.

RESULTS.

A significant increase (p>0.05) in frequencies between 45 and 55 Hz was observed in cobalt treated rats. Thirty minutes after HGF administration this increase began to disappeared and was completely absent 120 minutes later. Fifteen and sixty hours after the HGF administration a significant decrease in absolute power (p<0.02) was observed in rats treated with HGF. No significant changes were observed in rats not treated with HGF. During flash stimulation, the EEG showed sharp waves close to the stimulus which start in occipito - parietal regions and propagate to central and frontal regions. It was also observed that the ERBP was elevated in all regions, mainly in parieto occipital areas. A significant reduction of paroxysmal activity of the frontal and central regions of the treated group was observed 7 days after the HGF treatment, whereas no significant changes were detected in the control group.

CONCLUSIONS.

These results show a reduction in absolute power in alpha, beta and gamma bands, probably due to an improvement in gabaergic neuronal activity. During flash stimulation, a significant (p<0.001) reduction in propagation and band power related to flash was found in frontal and central regions, suggest less facility in recruitment and therefore a smaller tendency to propagate, which would reduce the probability of a crisis generalization.

CONTROL BEFORE SALINE ADMINISTRATION.