Analysis of Receptor’s Distribution in Entorhinal Cortex after Induction of Spreading Depression in Juvenile Rats

Spreading depression (SD), discovered by Leao in 1944, is a pathophysiological wave which propagates slowly in the brain (3 mm/min) and cause dramatic ionic and hemodynamic changes. SD appears to act through several mechanisms and receptors which have not completely understood. Here, we studied the effect of inhibitory system in animal model of SD using immunohistochemistry technique. After implanting recording electrodes and cannula over the brain, repetitive SD was induced by KCl injection (2 M) in juvenile rats for four consecutive weeks. Then all rats were decapitated and the brains removed. Mean number of dark neurons in entorhinal cortex were determined using Toluidine blue staining. To identify the prevalence and distribution of γ-aminobutyric acid A (GABA-A) subunit receptors and glutamic acid decarboxylase (GAD), immunohistochemistry technique was performed. The mean number of SD induced by KCl injection was statistically increased during four weeks of experiments (P=0.036). The mean number of dark neurons in entorhinal cortex was significantly increased in SD group compared to sham rats (P≤0.001). Also, expression of GAD 65 receptor in the Entorhinal cortex significantly increased in SD group compare to control group (P<0.05). GABA-Aα and GABA-Aβ receptors didn’t show significant change in that region. These data suggest that SD is able to damage neural cells and also it could lead to enhancement of GAD, the enzyme which is responsible for synthesizing an important inhibitory neurotransmitter, GABA receptor, in the central nervous system. Keywords: Cortical Spreading Depression, Entorhinal Cortex, Gamma-Aminobutyric Acid

Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York

Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York

Congenital Absence of the Posterior Element of C1, C2, and C3 Along with Bilateral Absence of C4 Pedicles: Case Report and Review of the Literature

Background: Abnormalities of the posterior arch of vertebrae are rare conditions that may incidentally be found on neck radiographs. We report a case and present a comprehensive review of the literature. Case Description: A 10-year-old boy presented with intermittent paresthesia in the lower extremities, mild neck pain, and episodes of drop attacks following neck flexion. Radiologic investigations depicted a complete absence of the posterior element of C1, C2, and C3 along with bilateral absence of C4 pedicles. Conclusions: The diagnosis of posterior arch abnormalities is of high-level of importance because of resultant neurologic defects. To the best of our knowledge, no case of this type has been reported in literature thus far. © 2017 Elsevier Inc

Congenital Absence of the Posterior Element of C1, C2, and C3 Along with Bilateral Absence of C4 Pedicles: Case Report and Review of the Literature

Background: Abnormalities of the posterior arch of vertebrae are rare conditions that may incidentally be found on neck radiographs. We report a case and present a comprehensive review of the literature. Case Description: A 10-year-old boy presented with intermittent paresthesia in the lower extremities, mild neck pain, and episodes of drop attacks following neck flexion. Radiologic investigations depicted a complete absence of the posterior element of C1, C2, and C3 along with bilateral absence of C4 pedicles. Conclusions: The diagnosis of posterior arch abnormalities is of high-level of importance because of resultant neurologic defects. To the best of our knowledge, no case of this type has been reported in literature thus far. © 2017 Elsevier Inc

Hippocampal serotonin-2A receptor-immunoreactive neurons density increases after testosterone therapy in the gonadectomized male mice

The change of steroid levels may also exert different modulatory effects on the number and class of serotonin receptors present in the plasma membrane. The effects of chronic treatment of testosterone for anxiety were examined and expression of 5-HT2A serotonergic receptor, neuron, astrocyte, and dark neuron density in the hippocampus of gonadectomized male mice was determined. Thirty-six adult male NMRI mice were randomly divided into six groups: intact-no testosterone treatment (No T), gonadectomy (GDX)-No T, GDX-Vehicle, GDX-6.25 mg/kg testosterone (T), GDX-12.5 mg/kg T, and GDX-25 mg/kg T. Anxiety-related behavior was evaluated using elevated plus maze apparatus. The animals were anesthetized after 48 hours after behavioral testing, and decapitated and micron slices were prepared for immunohistochemical as well as histopathological assessment. Subcutaneous injection of testosterone (25 mg/kg) may induce anxiogenic-like behavior in male mice. In addition, immunohistochemical data reveal reduced expression of 5-HT2A serotonergic receptor after gonadectomy in all areas of the hippocampus. However, treatment with testosterone could increase the mean number of dark neurons as well as immunoreactive neurons in CA1 and CA3 area, dose dependently. The density of 5-HT2A receptor-immunoreactive neurons may play a crucial role in the induction of anxiety like behavior. As reduction in such receptor expression have shown to significantly enhance anxiety behaviors. However, replacement of testosterone dose dependently enhances the number of 5-HT2A receptor-immunoreactive neurons and interestingly also reduced anxiety like behaviors. Copyright © 2016. Anatomy & Cell Biology

Discrepancies of Notch 1 receptor during development of chronic seizures

The critical role of Notch signaling has been shown in the pathogenesis of some neurological disorders including schizophrenia, epilepsy and Alzheimer�s disease. This study was aimed to evaluate the role of Notch 1 receptor in epileptogenesis as well as seizure characteristics. The animals were divided into three groups of sham, early stage and end stage. In sham group: Normal saline was injected intraperitoneally (ip) in the same as protocol of pentylenetetrazol (PTZ) injection. PTZ was injected (ip) every 48 hr over a period of 1 week in the group of early stage and over a period of 4 weeks in the end stage. The gene expression as well as distribution of Notch 1 receptor was assessed in the parietal cortex and hippocampus. In addition, the effect of agonist or antagonist of Notch 1 receptor was assessed on the epileptic discharges induced by PTZ injection. The gene expression of Notch 1 decreased in the hippocampus significantly in the end-stage group compared with sham, and early groups. Furthermore, distribution of Notch 1 receptor increased in the somatosensory cortex and decreased in the CA1 hippocampal area in the end-stage group. Intraventricular microinjection of Notch 1 agonist significantly increased the amplitude as well as frequency of spikes and decreased the latency of first epileptic discharges. Our findings illustrate the critical role of Notch signalling as a potential pathway in the epileptogenesis during development of chronic seizures. © 2019 Wiley Periodicals, Inc