scholarly journals Prolonged Therapeutic Hypothermia does not Adversely Impact Neuroplasticity after Global Ischemia in Rats

2012 ◽  
Vol 32 (8) ◽  
pp. 1525-1534 ◽  
Author(s):  
Gergely Silasi ◽  
Ana C Klahr ◽  
Mark J Hackett ◽  
Angela M Auriat ◽  
Helen Nichol ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Tissue Injury ◽  
Vessel Occlusion ◽  
X Ray ◽  
Animal Data ◽  
Hippocampal Ca1 ◽  
Occlusion Model ◽  
Neurotropic Factor ◽  
Normothermic Group ◽  
Unilateral Brain

Hypothermia improves clinical outcome after cardiac arrest in adults. Animal data show that a day or more of cooling optimally reduces edema and tissue injury after cerebral ischemia, especially after longer intervention delays. Lengthy treatments, however, may inhibit repair processes (e.g., synaptogenesis). Thus, we evaluated whether unilateral brain hypothermia (∼33°C) affects neuroplasticity in the rat 2-vessel occlusion model. In the first experiment, we cooled starting 1 hour after ischemia for 2, 4, or 7 days. Another group was cooled for 2 days starting 48 hours after ischemia. One group remained normothermic throughout. All hypothermia treatments started 1 hour after ischemia equally reduced hippocampal CA1 injury in the cooled hemisphere compared with the normothermic side and the normothermic group. Cooling only on days 3 and 4 was not beneficial. Importantly, no treatment influenced neurogenesis (Ki67/Doublecortin (DCX) staining), synapse formation (synaptophysin), or brain-derived neurotropic factor (BDNF) immunohistochemistry. A second experiment confirmed that BDNF levels (ELISA) were equivalent in normothermic and 7-day cooled rats. Last, we measured zinc (Zn), which is important in plasticity, with X-ray fluorescence imaging in normothermic and 7-day cooled rats. Hypothermia did not alter the postischemic distribution of Zn within the hippocampus. In summary, cooling significantly mitigates injury without compromising neuroplasticity.

A modified four vessel occlusion model of global cerebral ischemia in rats

2021 ◽  
Vol 352 ◽  
pp. 109090
Author(s):  
Wei Sun ◽  
Yeting Chen ◽  
Yongjie Zhang ◽  
Yue Geng ◽  
Xiaohang Tang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Global Cerebral Ischemia ◽  
Vessel Occlusion ◽  
Occlusion Model

scholarly journals Emergence of Non-Canonical Parvalbumin-Containing Interneurons in Hippocampus of a Murine Model of Type I Lissencephaly

2020 ◽  
Author(s):  
Tyler G. Ekins ◽  
Vivek Mahadevan ◽  
Yajun Zhang ◽  
James A. D’Amour ◽  
Timothy Petros ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Brain Structures ◽  
Cellular Migration ◽  
Morphological Development ◽  
Type I ◽  
Hippocampal Ca1 ◽  
Migration Disorder ◽  
Fast Spiking ◽  
And Control ◽  
The Impact

ABSTRACTType I lissencephaly is a neuronal migration disorder caused by haploinsuffiency of the LIS1 gene and is characterized in humans by agyria, mislamination of brain structures, developmental delays, and epilepsy. Here, we investigate the impact of LIS1 mutation on the cellular migration, morphophysiology, microcircuitry and genomics of mouse hippocampal CA1 parvalbumin-containing inhibitory interneurons (PV+INTs). We find that WT PV+INTs consist of two physiological subtypes (80% fast-spiking (FS), 20% non-fast-spiking (NFS)) and four morphological subtypes (basket, axo-axonic, bistratified, radiatum-targeting). We also discover that cell-autonomous mutations within interneurons disrupts morphological development of PV+INTs and results in the emergence of a non-canonical “intermediate spiking (IS)” subset of PV+INTs. In the GlobalLis mutant, IS/NFS cells become the dominant PV+INT subtypes (56%) and the percentage of FS cells shrinks to 44%. We also find that IS/NFS cells are prone to entering depolarizing block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures. Finally, single-cell nuclear RNAsequencing of PV+INTs revealed several misregulated genes related to morphogenesis, cellular excitability, and synapse formation.

Abstract WP437: Shear-activated Nanoparticle Aggregate Lysis Combined With Temporary Stent-bypass to Treat Emergent Large Vessel Occlusions (ELVO)

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Miklos G Marosfoi ◽  
Netanel Korin ◽  
Matthew J Gounis ◽  
Oktay Uzun ◽  
Srinivasan Vedantham ◽  
...  
Keyword(s):  
Vascular Injury ◽  
Targeted Delivery ◽  
Vascular Trauma ◽  
Stent Retriever ◽  
Arterial Infusion ◽  
Vessel Occlusion ◽  
Occlusion Model ◽  
Stent Retrievers ◽  
Endovascular Approach ◽  
Temporary Stent

Introduction: Despite the high effectiveness of stent-retrievers in ELVO, half of the patients remained functionally dependent (mRS≥3) after 90-days. Beyond futile recanalizations, variable endoluminal damage caused by stent-retrievers may contribute to reperfusion injury, and recruit iniflammatory cell infiltration. The goal of this study was to assess a less traumatic endovascular approach in combination with a novel shear activated-nanotherapeutic (SA-NT) that releases r-tPA when exposed to high levels of hemodynamic stress. Hypothesis: SA-NT treatment coupled with temporary endovascular bypass provides high recanalization rates while reducing vascular injury. Methods: a rabbit carotid vessel occlusion model was used. We evaluated angiographic recanalization with stent-bypass alone, intra-arterial delivery of soluble r-tPA alone, or stent-bypass combined with two doses (2 and 20 mg r-tPA) of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy by assessing the level of damage on histology. Results: Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared to controls (p=0.0011). SA-NT (20mg) had a higher likelihood of obtaining complete recanalization (mTICI:3) as compared to stent-bypass alone (OR: 65.019,95%CI:[1.77,>1000], p=0.0231), intra-arterial r-tPA alone (OR: 65.019, 95% CI [1.77,>1000], p=0.0231), or stent-bypass with soluble r-tPA (2 mg) (OR: 18.78, 95%CI [1.28,275.05], p=0.0322) (Figure). Histologically, there was significantly less vascular injury using a stent-bypass as compared to stent-retriever procedure (OR 12.97, 95%CI [8.01,21.02], p<0.0001). Conclusion: Nanoparticle-based thrombolytic therapy combined with stent-bypass achieves high rates of complete (mTICI:3) recanalization. This technology reduces vascular trauma as compared to stent-retriever thrombectomy

Aloe veramodulates X-ray induced hematological and splenic tissue damage in mice

2019 ◽  
Vol 38 (10) ◽  
pp. 1195-1211
Author(s):  
S Bala ◽  
NA Chugh ◽  
SC Bansal ◽  
A Koul
Keyword(s):  
Defense Mechanism ◽  
Tissue Injury ◽  
Hematological Parameters ◽  
Aloe Vera ◽  
Splenic Tissue ◽  
Whole Body ◽  
Control Group ◽  
Lactate Dehydrogenase Activity ◽  
X Ray ◽  
Cell Counts

The present study was premeditated to examine the radioprotective effects of aqueous Aloe vera gel extract against whole-body X-ray irradiation–induced hematological alterations and splenic tissue injury in mice. Healthy male balb/c mice were divided into four groups: group 1, control; group 2, A. vera (50 mg/kg body weight) administered per oral on alternate days for 30 days (15 times); group 3, X-ray exposure of 2 Gy (0.25 Gy twice a day for four consecutive days in the last week of the experimental protocol); and group 4, A. vera + X-ray. X-ray exposure caused alterations in histoarchitecture of spleen along with enhanced clastogenic damage as assessed by micronucleus formation and apoptotic index. Irradiation caused an elevation in proinflammatory cytokines like tumor necrosis factor and interleukin-6, total leucocyte counts, neutrophil counts and decreased platelet counts along with unaltered red blood cell counts and hemoglobin. Irradiation also caused an elevation in reactive oxygen species (ROS), lipid peroxidation (LPO) levels, lactate dehydrogenase activity and alterations in enzymatic and nonenzymatic antioxidant defense mechanism in plasma and spleen. However, administration of A. vera gel extract ameliorated X-ray irradiation–induced elevation in ROS/LPO levels, histopathological and clastogenic damage. It also modulated biochemical indices, inflammatory markers, and hematological parameters. These results collectively indicated that the A. vera gel extract offers protection against whole-body X-ray exposure by virtue of its antioxidant, anti-inflammatory and anti-apoptotic potential.

scholarly journals The Role of Glutamate Release on Voltage-Dependent Anion Channels (VDAC)-Mediated Apoptosis in an Eleven Vessel Occlusion Model in Rats

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15192 ◽  
Author(s):  
Eunkuk Park ◽  
Gi-Ja Lee ◽  
Samjin Choi ◽  
Seok-Keun Choi ◽  
Su-Jin Chae ◽  
...  
Keyword(s):  
Glutamate Release ◽  
Anion Channels ◽  
Vessel Occlusion ◽  
Occlusion Model ◽  
Voltage Dependent

scholarly journals Roles of NAD+, PARP-1, and Sirtuins in Cell Death, Ischemic Brain Injury, and Synchrotron Radiation X-Ray-Induced Tissue Injury

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Weihai Ying
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Synchrotron Radiation ◽  
Brain Damage ◽  
Tissue Injury ◽  
Ischemic Brain Injury ◽  
Biological Processes ◽  
Ischemic Brain ◽  
X Ray ◽  
Parp 1

NAD+plays crucial roles in a variety of biological processes including energy metabolism, aging, and calcium homeostasis. Multiple studies have also shown that NAD+administration can profoundly decrease oxidative cell death and ischemic brain injury. A number of recent studies have further indicated that NAD+administration can decrease ischemic brain damage, traumatic brain damage and synchrotron radiation X-ray-induced tissue injury by such mechanisms as inhibiting inflammation, decreasing autophagy, and reducing DNA damage. Our latest study that applies nano-particles as a NAD+carrier has also provided first direct evidence demonstrating a key role of NAD+depletion in oxidative stress-induced ATP depletion. Poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins are key NAD+-consuming enzymes that mediate multiple biological processes. Recent studies have provided new information regarding PARP-1 and sirtuins in cell death, ischemic brain damage and synchrotron radiation X-ray-induced tissue damage. These findings have collectively supported the hypothesis that NAD+metabolism, PARP-1 and sirtuins play fundamental roles in oxidative stress-induced cell death, ischemic brain injury, and radiation injury. The findings have also supported “the Central Regulatory Network Hypothesis”, which proposes that a fundamental network that consists of ATP, NAD+and Ca2+as its key components is the essential network regulating various biological processes.

scholarly journals Endothelin Levels Increase in Rat Focal and Global Ischemia

1994 ◽  
Vol 14 (2) ◽  
pp. 337-342 ◽  
Author(s):  
F. C. Barone ◽  
M. Y.-T. Globus ◽  
W. J. Price ◽  
R. F. White ◽  
B. L. Storer ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Vascular Function ◽  
Tissue Injury ◽  
Extracellular Fluid ◽  
Artery Occlusion ◽  
Global Ischemia ◽  
Vessel Occlusion ◽  
Cerebral Artery Occlusion

Endothelin-1, a peptide exhibiting extremely potent cerebral vasoactive properties, is elevated in the cerebrospinal fluid after hemorrhagic stroke and implicated in cerebral vasospasm. The purpose of this study was to determine changes in endothelin in ischemic rat brain by assaying endothelin tissue and extracellular levels. Immunoreactive endothelin levels in ischemic brain tissue following permanent or transient focal ischemia produced by middle cerebral artery occlusion was determined. In addition, endothelin levels were assayed in striatal extracellular fluid collected by microdialysis before, during, and after global ischemia produced by two-vessel occlusion combined with hypotension. Twenty-four hours after the onset of permanent middle cerebral artery occlusion, the ischemic cortex level (0.58 ± 0.27 fmol/mg protein) of immunoreactive endothelin was significantly (p < 0.05) increased, by 100%, over that in the nonischemic cortex (0.29 ± 0.13 fmol/mg protein). Transient artery occlusion for 80 min with reperfusion for 24 h also resulted in a similar significant (p < 0.05) increase, 78%, in immunoreactive endothelin in the ischemic zone. Global forebrain ischemia significantly (p < 0.05) increased the level of immunoreactive endothelin collected in striatal microdialysis perfusate, from a basal level of 14.6 ± 6.7 to 26.5 ± 7.7 and 26.2 ± 7.4 amol/μl (i.e. 82 and 79%). These changes reflect the relative picomolar extracellular concentration increases during ischemia and following reperfusion, respectively. This is the first demonstration of elevated levels of endothelin in focal ischemic tissue and in the extracellular fluid in global ischemia and suggests a role of the peptide in ischemic and postischemic derangements of cerebral vascular function and tissue injury.

Sign in / Sign up

Export Citation Format

Share Document