scholarly journals Myoinositol Attenuates the Cell Loss and Biochemical Changes Induced by Kainic Acid Status Epilepticus

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Lia Tsverava ◽  
Tamar Lordkipanidze ◽  
Eka Lepsveridze ◽  
Maia Nozadze ◽  
Marina Kikvidze ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Kainic Acid ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Cell Loss ◽  
Biochemical Changes ◽  
Time Schedule ◽  
Biochemical Processes ◽  
Voltage Dependent ◽  
Acid Status

Identification of compounds preventing or modifying the biochemical changes that underlie the epileptogenesis process and understanding the mechanism of their action are of great importance. We have previously shown that myoinositol (MI) daily treatment for 28 days prevents certain biochemical changes that are triggered by kainic acid (KA) induced status epilepticus (SE). However in these studies we have not detected any effects of MI on the first day after SE. In the present study we broadened our research and focused on other molecular and morphological changes at the early stages of SE induced by KA and effects of MI treatment on these changes. The increase in the amount of voltage-dependent anionic channel-1 (VDAC-1), cofilin, and caspase-3 activity was observed in the hippocampus of KA treated rats. Administration of MI 4 hours later after KA treatment abolishes these changes, whereas diazepam treatment by the same time schedule has no significant influence. The number of neuronal cells in CA1 and CA3 subfields of hippocampus is decreased after KA induced SE and MI posttreatment significantly attenuates this reduction. No significant changes are observed in the neocortex. Obtained results indicate that MI posttreatment after KA induced SE could successfully target the biochemical processes involved in apoptosis, reduces cell loss, and can be successfully used in the future for translational research.

Genetic background regulates semaphorin gene expression and epileptogenesis in mouse brain after kainic acid status epilepticus

Neuroscience ◽  
2005 ◽  
Vol 131 (4) ◽  
pp. 853-869 ◽  
Author(s):  
J. Yang ◽  
B. Houk ◽  
J. Shah ◽  
K.F. Hauser ◽  
Y. Luo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Status Epilepticus ◽  
Kainic Acid ◽  
Mouse Brain ◽  
Genetic Background ◽  
Acid Status

The Protective Effect of Myo-inositol on Hippocamal Cell Loss and Structural Alterations in Neurons and Synapses Triggered by Kainic Acid-Induced Status Epilepticus

2013 ◽  
Vol 33 (5) ◽  
pp. 659-671 ◽  
Author(s):  
Nato Kotaria ◽  
Maia Kiladze ◽  
Mzia G. Zhvania ◽  
Nadezhda J. Japaridze ◽  
Tamar Bikashvili ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Protective Effect ◽  
Kainic Acid ◽  
Cell Loss ◽  
Structural Alterations

scholarly journals Inhibiting HIF-1α Decreases Expression of TNF-α and Caspase-3 in Specific Brain Regions Exposed Kainic Acid-Induced Status Epilepticus

2016 ◽  
Vol 38 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Jixue Yang ◽  
Fang He ◽  
Qiang Meng ◽  
Yang Sun ◽  
Weiwen Wang ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Kainic Acid ◽  
Parietal Cortex ◽  
Caspase 3 ◽  
Hypoxia Inducible Factor ◽  
Brain Regions ◽  
Epileptic Activity ◽  
Vehicle Control ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Background/Aims: A recent study demonstrates that pro-inflammatory cytokines (PICs, i.e., IL-1β, IL-6 and TNF-α) in specific brain regions of rats play a role in regulating kainic acid (KA)-induced status epilepticus (SE) via a GABAergic mechanism. The purposes of this report were to examine contributions of hypoxia inducible factor subtype 1α (HIF-1α) to expression of PICs in these specific brain regions in epileptic rats. Particularly, we investigated the parietal cortex, hippocampus and amygdala. In addition, we further examined expression of Caspase-3 indicating cell apoptosis in those brain regions of epileptic rats after infusing 2-methoxyestradiol (2-MET, inhibitor of HIF-1α) and etanercept (TNF-α receptor antagonist). Methods: ELISA was used to determine the levels of HIF-1α and PICs and western blot analysis was used to examine Caspase-3 expression. Results: Our data show that HIF-1α was significantly increased in the parietal cortex, hippocampus and amygdala 1, 3 and 7 days after induction of SE (P<0.05 vs. control rats). Our results also show that inhibiting HIF-1α by central infusion of 2-MET significantly decreased the amplified TNF-α expression in these brain regions evoked by SE (P<0.05 vs. vehicle control), but did not modify IL-1β and IL-6. Our results demonstrate that 2-MET and etanercept attenuated an increase in Caspase-3 evoked by SE. Conclusion: Overall, we suggest that HIF-1α activated by SE is likely to contribute to epileptic activity via a TNF-α pathway, which has pharmacological implications to target specific HIF-1α and TNF-α pathways for neuronal dysfunction and vulnerability related to epilepsy.

scholarly journals Tualang Honey Reduced Neuroinflammation and Caspase-3 Activity in Rat Brain after Kainic Acid-Induced Status Epilepticus

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Nur Shafika Mohd Sairazi ◽  
Kuttulebbai N. S. Sirajudeen ◽  
Mustapha Muzaimi ◽  
Swamy Mummedy ◽  
Mohd Asnizam Asari ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Status Epilepticus ◽  
Kainic Acid ◽  
Caspase 3 ◽  
Brain Regions ◽  
Multiple Time ◽  
Time Points ◽  
Cox 2 ◽  
Multiple Time Points ◽  
Tualang Honey

The protective effect of tualang honey (TH) on neuroinflammation and caspase-3 activity in rat cerebral cortex, cerebellum, and brainstem after kainic acid- (KA-) induced status epilepticus was investigated. Male Sprague-Dawley rats were pretreated orally with TH (1.0 g/kg body weight) five times at 12 h intervals. KA (15 mg/kg body weight) was injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Neuroinflammation markers and caspase-3 activity were analyzed in different brain regions 2 h, 24 h, and 48 h after KA administration. Administration of KA induced epileptic seizures. KA caused significant (p < 0.05) increase in the level of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), glial fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF-1), and cyclooxygenase-2 (COX-2) and increase in the caspase-3 activity in the rat cerebral cortex, cerebellum, and brainstem at multiple time points. Pretreatment with TH significantly (p < 0.05) reduced the elevation of TNF-α, IL-1β, GFAP, AIF-1, and COX-2 level in those brain regions at multiple time points and attenuated the increased caspase-3 activity in the cerebral cortex. In conclusion, TH reduced neuroinflammation and caspase-3 activity after kainic acid- (KA-) induced status epilepticus.

scholarly journals Caspase-mediated Cleavage of p130cas in Etoposide-induced Apoptotic Rat-1 Cells

2000 ◽  
Vol 11 (3) ◽  
pp. 929-939 ◽  
Author(s):  
Seunghyi Kook ◽  
Sang Ryeol Shim ◽  
Soo Jeon Choi ◽  
Joohong Ahnn ◽  
Jae Il Kim ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Focal Adhesion ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Point Mutations ◽  
Membrane Blebbing ◽  
Adhesion Sites ◽  
Focal Adhesion Proteins ◽  
Induced Apoptosis

Apoptosis causes characteristic morphological changes in cells, including membrane blebbing, cell detachment from the extracellular matrix, and loss of cell–cell contacts. We investigated the changes in focal adhesion proteins during etoposide-induced apoptosis in Rat-1 cells and found that during apoptosis, p130cas (Crk-associated substrate [Cas]) is cleaved by caspase-3. Sequence analysis showed that Cas contains 10 DXXD consensus sites preferred by caspase-3. We identified two of these sites (DVPD416G and DSPD748G) in vitro, and point mutations substituting the Asp of DVPD416G and DSPD748G with Glu blocked caspase-3-mediated cleavage. Cleavage at DVPD416G generated a 74-kDa fragment, which was in turn cleaved at DSPD748G, yielding 47- and 31-kDa fragments. Immunofluorescence microscopy revealed well-developed focal adhesion sites in control cells that dramatically declined in number in etoposide-treated cells. Cas cleavage correlated temporally with the onset of apoptosis and coincided with the loss of p125FAK (focal adhesion kinase [FAK]) from focal adhesion sites and the attenuation of Cas–paxillin interactions. Considering that Cas associates with FAK, paxillin, and other molecules involved in the integrin signaling pathway, these results suggest that caspase-mediated cleavage of Cas contributes to the disassembly of focal adhesion complexes and interrupts survival signals from the extracellular matrix.

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