Cortical Bilateral Adaptations in Rats Submitted to Focal Cerebral Ischemia: Emphasis on Glial Metabolism

Abstract

This study was performed to evaluate the bilateral effects of focal permanent ischemia (FPI) on glial metabolism in the cerebral cortex. Two and 9 days after FPI induction, we analyze [F]FDG metabolism by micro-PET, astrocyte morphology and reactivity by immunohistochemistry, cytokines and trophic factors by ELISA, glutamate transporters by RT-PCR, monocarboxylate transporters (MCTs) by western blot, and substrate uptake and oxidation by ex vivo slices model. The FPI was induced surgically by thermocoagulation of the blood in the pial vessels of the motor and sensorimotor cortices in adult (90 days old) male Wistar rats. Neurochemical analyses were performed separately on both ipsilateral and contralateral cortical hemispheres. In both cortical hemispheres, we observed an increase in tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and glutamate transporter 1 (GLT-1) mRNA levels; lactate oxidation; and glutamate uptake and a decrease in brain-derived neurotrophic factor (BDNF) after 2 days of FPI. Nine days after FPI, we observed an increase in TNF-α levels and a decrease in BDNF, GLT-1, and glutamate aspartate transporter (GLAST) mRNA levels in both hemispheres. Additionally, most of the unilateral alterations were found only in the ipsilateral hemisphere and persisted until 9 days post-FPI. They include diminished in vivo glucose uptake and GLAST expression, followed by increased glial fibrillary acidic protein (GFAP) gray values, astrocyte reactivity, and glutamate oxidation. Astrocytes presented signs of long-lasting reactivity, showing a radial morphology. In the intact hemisphere, there was a decrease in MCT2 levels, which did not persist. Our study shows the bilateralism of glial modifications following FPI, highlighting the role of energy metabolism adaptations on brain recovery post-ischemia.

Evaluation of temperature induction in focal ischemic thermocoagulation model

“…This parameter is not used often in preclinical experiments [ 38 , 39 ], but the increased interest in clinical studies about brain heat after deep brain stimulation for the treatment of medically refractory movement disorders as well as other neurological and psychiatric conditions [ 40 ] go back to the preclinical studies about the thermal impact of implants on brain tissue. Nonose et al, (2017) [ 13 ] showed metabolic changes (glutamate uptake and lactate oxidation) at near and far cortical areas after increased thermal induction. Therefore, the heat transfer control is a pivotal aspect in this ischemic model.…”

Peripheral Oxidative Stress Biomarkers in Spinocerebellar Ataxia Type 3/Machado–Joseph Disease

“…The Ζ -score was calculated using the following formula: where x is the sample value (raw score), μ is the population mean, and σ is the standard deviation of the population. The absolute value of Ζ represents the distance between the raw score and the population mean in units of SD ( 31 ).…”

The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke

“…But injured CNS neurons can benfit from active or passive immunization with CNS myelin‐associated antigens. Peripheral immune cell infiltration and inflammation in the ischemic brain also drastically changes the microenvironment for brain repair and impairs the proneurogenic homeostasis after stroke, which is believed to be a prerequisite for the development, and survival of de novo generated neurons . In the ischemic stroke model, the neurogenesis after stroke also depends on T lymphocytes subgroups, different subgroup deficient plays different effect on neurogenesis .…”

“…Although astrocytes are not typical immune cells, they can function as inflammatory cells and produce inflammatory factors affecting the post–stroke immune responses . In addition, astrocytes provide energy and structural support, glucose metabolism, take up excessive molecules in the extracellular matrix, and actively participate in neuronal proliferation, maturation, and survival . They stimulate neurogenesis by secreting prodifferentiation factors such as Wnt and proproliferation factors such as insulin growth factors (IGF), BDNF, glia‐derived neurotrophic factor (GDNF), nerve growth factor (NGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), ciliary neurotrophic factor (CNTF), and erythropoietin (EPO) .…”