Abstract P775: Ascorbate Prevents Secondary Brain Damage Following Stroke Through Epigenetic Gene Regulation

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Kahlilia Morris-Blanco ◽  
TaeHee Kim ◽  
Anil Chokkalla ◽  
Mario Bertogliat ◽  
Raghu Vemuganti
Keyword(s):  
Brain Damage ◽  
Motor Function ◽  
Epigenetic Modification ◽  
Experimental Stroke ◽  
Intracerebral Injection ◽  
Sequencing Analysis ◽  
Secondary Brain Damage ◽  
Male And Female ◽  
Stroke Treatment ◽  
Female Mice

The antioxidant ascorbate is an enzyme cofactor with established roles in maintaining brain function and providing neuroprotection in response to oxidative stress. Recently ascorbate has been identified as an epigenetic regulator through its ability to induce the activity of the ten-eleven translocase (TET) enzymes that produce 5-hydroxymethylcytosine (5-hmC), a CNS-enriched epigenetic modification that is associated with transcriptional activation and neuroprotection. In the current study, we evaluated the role of ascorbate on 5-hmC and its therapeutic potential against ischemic brain injury in comorbid conditions associated with stroke in mice. Adult mice subjected to transient middle cerebral artery occlusion (MCAO) were injected intraperitoneally (i.p.) with ascorbate at 30 min of reperfusion. Young adult male and female mice showed robust induction of 5hmC in the peri-infarct region of the cortex, reduced infarct size and improved motor function. Knockdown of TET3 by intracerebral injection using siRNA blocked the ascorbate-induced increases in 5hmC and led to increased brain degeneration and motor function deficits. Genome-wide sequencing analysis of differentially hydroxymethylated regions (DhMRs) revealed that ascorbate increased 5hmC at the promoters of genes associated with protection against ischemia pathophysiology. Furthermore, ascorbate treatment reduced infarct and improved functional recovery in aged, obese diabetic and hypertensive male and female mice. Delayed ascorbate treatment at 6h of reperfusion was also protective against secondary brain damage and motor deficits following experimental stroke. Collectively, these results indicate that ascorbate regulates the 5hmC epigenetic modification in a neuroprotective manner and may represent a promising therapeutic target for stroke treatment.

Abstract T P210: Splenectomy Attenuates Sex Differences in Infarct Volume Following Experimental Stroke in Mice

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Jianming Wang ◽  
Sheetal Bodhankar ◽  
Halina Offner ◽  
Stephanie J Murphy
Keyword(s):  
Sex Differences ◽  
Blood Glucose ◽  
Brain Injury ◽  
Infarct Volume ◽  
Blood Gases ◽  
Experimental Stroke ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Male And Female ◽  
Female Mice

It is now increasingly clear that human stroke can have other serious consequences besides brain damage that can impact on patient survival and recovery. For example, many stroke patients succumb to CNS injury-induced immunodepression and fatal infections. Our prior work suggests that evolving cerebral ischemic injury elicits a cycle of injury from brain-to-spleen-to-brain that is strongly influenced by sex. We determined if splenic immunocytes are important in contributing to sex differences in post-ischemic brain injury. Male and female C57BL/6J mice were splenectomized 14 days before experimental stroke. Male and female mice with or without splenectomy (n=9-10 per group) then underwent 60 min of middle cerebral artery occlusion (MCAO) via intraluminal filament. Laser-Doppler flowmetry (LDF) was used to monitor cortical perfusion. All mice were euthanized and brains collected at 96 hours of reperfusion. Infarct volume (% corrected contralateral structure) was determined by image analysis of coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride. Mean arterial blood pressure (MABP), blood gases (pH, P a O 2 , P a CO 2 ), and blood glucose were measured at 30 min MCAO and at 15 min of reperfusion in separate groups of male and female mice with or without splenectomy (n=5 per group). Relative LDF changes (% baseline), MABP, blood gases, and blood glucose during and after MCAO were comparable among the experimental groups. We observed that infarct volume in females (cortex, 41±4%; striatum, 55±6%) was smaller ( P <0.05) compared to males (cortex, 52±3%; striatum, 75±3%) at 96 hours of reperfusion. However, no differences (cortex, P =0.313; striatum, P =0.601) in infarct volume were seen between splenectomized male (cortex, 43±4%; striatum, 51±7%) and female (cortex, 38±4%; striatum, 46±5%) mice. Our data suggest that removal of all splenocyte lineages via splenectomy attenuates sex differences in post-ischemic brain injury. Future studies will evaluate the role of different splenic immunocyte subsets, such as T or B lymphocytes, on male vs. female ischemic brain outcomes. This study was supported by National Institutes of Health grant NS076013.

scholarly journals Transcriptional Analysis Shows a Robust Host Response toToxoplasma gondiiduring Early and Late Chronic Infection in Both Male and Female Mice

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Andrew L. Garfoot ◽  
Patrick W. Cervantes ◽  
Laura J. Knoll
Keyword(s):  
Chronic Infection ◽  
Host Response ◽  
Differentially Expressed ◽  
Transcriptional Analysis ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Male And Female ◽  
Content Type ◽  
Female Mice ◽  
Host Genes

ABSTRACTThe long-term host effects caused by the protozoan parasiteToxoplasma gondiiare poorly understood. High-throughput RNA sequencing analysis previously determined that the host response in the brain was greater and more complex at 28 days than at 10 days postinfection. Here, we analyzed the host transcriptional profile of age- and sex-matched mice during very early (21 days), early (28 days), mid (3 months), and late (6 months) chronic infection. We found that a majority of the host genes which increase in abundance at day 21 postinfection are still increased at 6 months postinfection for both male and female mice. While most of the differentially expressed genes were similar between sexes, females had far fewer genes that were significantly less abundant, which may have led to the slightly increased cyst burden in males. Transcripts for C-X-C motif chemokine ligand 13 and a C-C motif chemokine receptor 2 (CCR2) were significantly higher in females than in males during infection. AsT. gondiichronic infection and profilin (PRF) confer resistance toListeria monocytogenesinfection in a CCR2-dependent manner, the differences in CCR2 expression led us to retest the protection of PRF in both sexes. Male mice were nearly as effective as female mice at reducing the bacterial burden either with a chronic infection or when treated with PRF. These data show that most of the host genes differentially expressed in response toT. gondiiinfection are similar between males and females. While differences in transcript abundance exist between the sexes, the infection phenotypes tested here did not show significant differences.

A subchronic oral toxicity study on medical herb extract, KIOM CRC#BP10A, in male and female mice

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
ES Cho ◽  
YJ Lee ◽  
JS Park ◽  
J Kim ◽  
NS Kim ◽  
...  
Keyword(s):  
Toxicity Study ◽  
Oral Toxicity ◽  
Male And Female ◽  
Female Mice ◽  
Subchronic Oral Toxicity Study ◽  
Herb Extract

Early Life Exposure to Antibiotic Alters Energy Balance during Chronic High-Fat Feeding in Adult Male and Female Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1999-P ◽  
Author(s):  
HYE LIM NOH ◽  
SUJIN SUK ◽  
RANDALL H. FRIEDLINE ◽  
KUNIKAZU INASHIMA ◽  
DUY A. TRAN ◽  
...  
Keyword(s):  
Energy Balance ◽  
Adult Male ◽  
Early Life ◽  
High Fat ◽  
Male And Female ◽  
Female Mice ◽  
Early Life Exposure ◽  
Fat Feeding

Comparison of Antinociceptive Effects Induced by Kappa Opioid Agonists in Male and Female Mice

Analgesia ◽  
1999 ◽  
Vol 4 (3) ◽  
pp. 397-404 ◽  
Author(s):  
Corinne A. Patrick ◽  
M. C. Holden Ko ◽  
James H. Woods
Keyword(s):  
Kappa Opioid ◽  
Male And Female ◽  
Female Mice ◽  
Opioid Agonists ◽  
Antinociceptive Effects

Maternal separation affects the electrophysiological properties of Aδ‐fibres and nociceptive behaviours in male and female mice

2020 ◽  
Vol 80 (6) ◽  
pp. 538-546
Author(s):  
Nancy Paniagua ◽  
Rocío Girón ◽  
Carlos Goicoechea ◽  
Mª Isabel Martín‐Fontelles ◽  
Ana Bagues
Keyword(s):  
Maternal Separation ◽  
Male And Female ◽  
Electrophysiological Properties ◽  
Female Mice

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

scholarly journals Digging behavior discrimination test to probe burrowing and exploratory digging in male and female mice

2021 ◽  
Author(s):  
Heather L. Pond ◽  
Abigail T. Heller ◽  
Brian M. Gural ◽  
Olivia P. McKissick ◽  
Molly K. Wilkinson ◽  
...  
Keyword(s):  
Discrimination Test ◽  
Male And Female ◽  
Female Mice ◽  
Digging Behavior
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