Banca de DEFESA: IGOR RAFAEL PRAXEDES DE SALES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : IGOR RAFAEL PRAXEDES DE SALES
DATE: 19/12/2022
TIME: 09:00
LOCAL: https://meet.google.com/qmz-ohzu-scj
TITLE:

ANTISEIZURE ACTIVITY OF PHYTOCOMPLEXES AND CANNABIDIOL IN STATUS EPILEPTICUS MODEL IN MICE

KEY WORDS:

status epilepticus, natural products, hippocampus, pilocarpine and phytocannabinoids

PAGES: 120
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:

Placebo-controlled clinical trials show that cannabidiol (CBD) reduces seizure frequency, both convulsive
and non-convulsive, in patients with difficult-to-control epilepsy. Part of this effect depends on
pharmacokinetic interactions since in these studies, patients continue conventional antiseizure
medication. Furthermore, the CBD mechanism would reduce seizure frequency still unknown, especially
considering its affinity for endocannabinoid system receptors. Other phytocannabinoids, such as
tetrahydrocannabinol (THC), also modify the endocannabinoid system, altering synaptic transmission
and neuronal excitability. Thus, this thesis evaluated the antiseizure potential of Cannabis extracts with
different profiles of phytocannabinoids (phytocomplexes) on status epilepticus (SE), comparing their
responses with those observed after CBD. We worked with the hypothesis that phytocomplexes derived
from Cannabis, as they contain a variety of secondary metabolites, would be more effective in
controlling neuronal hyperexcitability than a pure phytocannabinoid (CBD). For this, we used
electrophysiological and behavioral recordings of mice submitted to the SE model induced by
pilocarpine intrahippocampal administration. Dose-response curves of two extracts, one with a
CBD/THC concentration ratio greater than 1 (XT-CBD) and the other with a CBD/THC ratio less than 1
(XT-THC), were compared with conventional treatments (e.g. , CBD and diazepam). The animals received
the experimental compound intraperitoneally (i.p.) thirty minutes before pilocarpine. We used the
ambulation between the two administrations as an indicator of possible sedative effects caused by the
extracts. Our results show that XT-CBD reduced the duration and severity of behavioral SE at all
evaluated doses (4, 36 and 360 mg/kg; n=6-9/group) compared to the control group (sterile corn oil
solution, 10 mL/kg; n=24, p<0.05, Mann-Whitney test). Treatment with XT-THC showed a biphasic
effect, with high doses (450 and 1000 mg/kg; n=6-9/group) decreasing the severity of seizures, while the
10 mg/kg dose (n=7 ) increased the proportion of animals with severe ictal behaviors. However, the high
doses of XT-THC produced strong sedation. Comparatively, the decrease in SE severity at high doses of
XT-CBD and XT-THC was similar to that observed in groups treated with diazepam (5 mg/kg; n=6; p>0.05;
Mann-Whitney test) and with CBD (200 mg/kg dose, n=11). Surprisingly, the treatment with CBD, XT-
THC and XT-CBD did not change macroscopic markers of electrographic paroxysms. Our results
demonstrate that phytocomplexes are effective in modulating the behavioral expression of
pharmacologically induced SE, and CBD rich extract are more effective than THC rich extracts. Future
experiments will be necessary to understand the dissociation between behavioral and electrographic
expression of phytocannabinoids on SE induced by intrahippocampal administration of pilocarpine.
Thereby, this study contributed to a better understanding of the use of phytocannabinoids in seizure
treatment.

COMMITTEE MEMBERS:
Externo à Instituição - FULVIO RIELI MENDES - UFABC
Externa à Instituição - BAGNÓLIA ARAÚJO DA SILVA - UFPB
Externa à Instituição - BRUNA DEL VECHIO KOIKE - UNIVASF
Presidente - 1728817 - CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
Interno - 2394627 - EDUARDO BOUTH SEQUERRA