Authors :
Presenting Author: Leonardo Vázquez-Morales, BSc – Intituto de Neurobiología, UNAM
Fernanda Guzman-Gómez, BS (expected) – UNAM
Deysi Gasca-Martinez, PhD – Intituto de Neurobiología, UNAM
Ericka de los Rios, PhD – Intituto de Neurobiología, UNAM
Luis Concha, PhD – Institito de Neurobiología, UNAM
Leonor Lopez-Meraz, PhD – Instituto de Investigaciones Cerebrales, UV
Hiram Luna-Munguia, PhD – Intituto de Neurobiologia, UNAM
Rationale:
Type 2 Diabetes Mellitus (T2DM) is characterized by chronic hyperglycemia and it has been associated to neurological impairments. Previous studies using diffusion tensor imaging have found microstructural changes in the patients’ brains. However, the timing of these abnormalities and how they may contribute to facilitate seizures or status epilepticus is still unclear (Chiewthanakul et al., 2015).
Methods:
Three-day-old Sprague-Dawley rat pups were divided in two groups: Control (vehicle sc injection; 9 males and 10 females) and streptozocin (STZ) (75 mg/kg sc injection; 22 males and 20 females). Glucose levels were evaluated every month until 4 months old. All animals were also scanned using a 7T MRI scanner at the same time points. Finally, all the animals received 3-mercaptopropionic acid (MP) every 12 h for 5 days to induce recurrent generalized seizures, followed by a crossed protocol with phenytoin for 4 days to assess pharmacorresistance. Every procedure adhered to the guidelines established by our Institutional Ethics Committee for Animal Use and Care (Protocol #154A) following the Official Mexican Standard NOM-062-ZOO-1999/SAGARPA.
Results:
Control animals showed blood glucose levels between 90 and 110 mg/dl. However, 11 male and 8 female STZ rats showed levels higher than 140 mg/dl since the second measurement, remaining elevated until the last one. Interestingly, these animals also showed a significant mean diffusivity increase in dorso-medial thalamus (2nd scan, p< 0.05), ventral hippocampus (3rd scan, p< 0.05), and cingulate (3rd scan, p< 0.05). Regarding fractional anisotropy, females showed significantly decreased values in internal capsule (3rd scan, p< 0.05), fimbria (4th scan, p< 0.01), and corpus callosum (4th scan, p< 0.01); males only showed a significant decrease in fimbria (3rd scan, p< 0.01). When submitted to the recurrent severe seizure model, the generalized seizures from both sexes tended to evolve to status epilepticus since the second MP administration. Moreover, pharmacoresistance was predominantly observed in the hyperglycemic group.
Conclusions:
This induction was considered indicative of high seizure severity, potentially attributable in part to hippocampal alterations (neuronal loss, gliosis) and reduced fractional anisotropy in specific brain regions, likely reflecting axonal degeneration.
Funding:
Acknowledgements: Imaging procedures were conducted at the National Laboratory for MRI. We thank Juan Ortiz and Mirelta Regalado for their technical assistance.
Funding: Supported by DGAPA-PAPIIT-UNAM (IN224523-HLM), CONACYT (FC1782-LC), and CONAHCYT scholarship (2052610-LVM).