hemopressin and Epilepsy

This study endeavoured to assess the effect of hemopressin (Hp), a nano peptide obtained from the alpha chain of hemoglobin, on chronic epileptic activity and its potential correlation with cannabinoid receptor type 1 (CB1). Male Wistar albino rats (230-260 g) were used. The kindling process was conducted by administering a sub-convulsant dose of pentylenetetrazol (PTZ) (35 mg/kg, i.p) three times a week for a maximum of 10 weeks. Tripolar electrodes and external cannula guides for intracerebroventricular (i.c.v) injections were surgically implanted in the skulls of kindled rats. On the day of the experiment, doses of Hp, AM-251, and ACEA were administered prior to the PTZ injections. Electroencephalography recordings and behavioural observations were conducted simultaneously for 30 min after the PTZ injection. The administration of Hp (0.6 μg, i.c.v) resulted in a decrease in epileptic activity. The CB1 receptor agonist ACEA (7.5 μg, i.c.v) showed an anticonvulsant effect, but the CB1 receptor antagonist AM-251 (0.5 μg, i.c.v) displayed a proconvulsant effect. The co-administration of Hp (0.6 μg, i.c.v) and ACEA (7.5 μg, i.c.v) and of Hp (0.6 μg, i.c.v) and AM-251 (0.5 μg, i.c.v) produced an anticonvulsant effect. However, when AM-251 was administered prior to Hp, it produced a proconvulsant impact that overrode Hp's intended anticonvulsant effect. Interestingly, the co-administration of Hp (0.03 μg) + AM-251 (0.125 μg) unexpectedly exhibited an anticonvulsant effect. Electrophysiological and behavioural evaluations demonstrated the anticonvulsant effect of Hp in the present model, highlighting the possibility that Hp may act as an agonist for the CB1 receptor.

Topics: Animals; Anticonvulsants; Cannabinoid Receptor Agonists; Cannabinoids; Dose-Response Relationship, Drug; Epilepsy; Hemoglobins; Male; Pentylenetetrazole; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1

Hemopressin (Hp) is the first peptide ligand described for the CB1 cannabinoid receptor. Therefore, we aimed to investigate the effect of hemopressin on pencillin-induced epileptiform activity by using electrophysiological recording (ECoG) technique.. Male Wistar rats were anesthetized with urethane (1.25 g/kg), and epileptiform activity was induced by intracortical injection of penicillin (500 IU). Animals were randomly divided into eight groups. Subsequently, the rats were administered with saline or hemopressin as follows: saline control group (Group I: 2 μl/i.c.v/saline), hemopressin groups (Group II: 0.025 μg/i.c.v; Group III: 0.075 μg/i.c.v; Group IV: 0.15 μg/i.c.v; Group V: 0.3 μg/i.c.v; Group VI: 0.6 μg/i.c.v; Group VII: 1.2 μg/i.c.v; Group VIII: 2.4 μg/i.c.v). The various doses of hemopressin were injected intracerebroventricularly (i.c.v) 30 minutes after penicillin (2.5μl) injection. After hemopressin injection, ECoGs were recorded for three hours.. Hp at doses of 0.075, 0.15, 0.3, 0.6, 1.2 and 2.4 μg/kg significantly increased the frequency of epileptiform ECoG activity compared to penicillin-injected group without changing the amplitude. The 0.6 µg hemopressin was the most effective dose to increase the epileptiform activity (p 0.05).. The results of this study provided electrophysiological evidence for hemopressin to be modulating penicillin-induced epileptiform activity by acting as CB1 receptor antagonist. Further studies are required to elucidate the involved mechanism underlying this effect (Fig. 3, Ref. 40).

Topics: Animals; Epilepsy; Hemoglobins; Male; Penicillins; Peptide Fragments; Random Allocation; Rats; Rats, Wistar