Texas A&M Translational and Experimental Stroke Research
About
We use experimental models to understand the short-term and long term consequences of ischemic stroke, and our goal is to develop stroke therapies, using compounds that can modify the brain and immune system, to improve stroke recovery.
We are especially interested in sex differences in stroke. Young females are less likely to experience a stroke as compared to young males. However, after the age of 50+, women are equally likely to suffer a stroke as compared to men. At older ages, many more women will get a stroke as compared to men, and their stroke are likely to be worse, resulting in greater mortality, disability and loss of independence. Women are also more likely to exhibit post-stroke depression.
Stroke outcomes can be modified by environmental and developmental factors, and in turn stroke can also lead to other disabilities, such as epilepsy, addiction, depression. In conjunction with our colleagues at the TAMHSC COM and TAMIN, we are studying these issues in an animal model.
Stroke therapies: We are discovering and testing drugs that can increase survival of neurons after stroke and reduce stroke-related disability. These compounds include peptide hormones, non-coding RNA and histone modifiers. Interestingly, many of these novel therapies are effective only in one sex.
Our stroke group and collaborators are seeking answers to this critical disease.
Stroke Group
Dr. Farida Sohrabji: PI, Professor
Dr. Shameena Bake: Research Assistant Professor
My research interest focuses on biological and environmental risk factors that affect neurovascular/blood-brain-barrier function in acute neurological disorders like stroke in adults. Particularly, I am interested in studying the cellular components of blood brain barrier /molecular mechanisms that are altered due to cerebral ischemia in the adult brain.
Min Jung Park: WHIN post doctoral Scholar
My current work in Dr. Farida Sohrabji's laboratory focuses on epigenetic changes in aging and innovative therapeutic strategies involving histone modifying agents for stroke recovery. Although clinical evidence shows aged women as likely to have higher risk, worse outcomes and poorer recovery from stroke compared to aged men, therapeutic interventions for stroke in aged females remain elusive. Hence, my project employed an HDAC inhibitor derived from short chain fatty acid, sodium butyrate (NaB), with the potential of improve stroke outcomes in aged females. I further investigate the roles of NaB in histone acetylation and DNA methylation both in central and peripheral tissues. Another arm of my project is to investigate the interactions between estrogen deficiency and gut microbiome among acute brain disorders, ischemic stroke. My two main hypotheses are (1) Estrogen deficiency produces gut dysbiosis that accelerates gut leakiness, BBB breakdown, and central and peripheral immune activation, which worsens stroke outcome/severity in the middle-aged female group; and (2) Restoring a healthy gut microbiota improves stroke outcome in middle-aged females.
Publications
- Chisholm NC, Henderson ML, Selvamani A, Park MJ, Dindot S, Miranda RC, Sohrabji F (2015) Histone methylation patterns in astrocytes are influenced by age following ischemia. Epigenetics 10:142-152. (PMCID: PMC4622874)
- Park MJ, Sohrabji F (2016) The histone deacetylase inhibitor, sodium butyrate, exhibits neuroprotective effects for ischemic stroke in middle-aged female rats. J Neuroinflammation 13:300. (PMCID: PMC5131416)
- Reddy DS, Bhimani A, Kuruba R, Park MJ, Sohrabji F (2016) Prospects of modeling poststroke epileptogenesis. Journal of neuroscience research. (PMCID: PMC5266751)
- Sohrabji F, Park MJ, Mahnke AH (2017) Sex differences in stroke therapies. Journal of neuroscience research 95:681-691. (PMCID: PMC5125551)
Andre Okoreeh: MD/PhD graduate program
Aditya Panta: MD/PhD graduate program
Post Stroke Depression:
In women, after menopause, stroke leads to greater disability in physical, communicative, cognitive, and emotional function. Women are also more likely to transfer to nursing homes and assisted care facilities, increasing the potential for social isolation. All these outcomes result in a poorer quality of life and make female stroke survivors more susceptible to post-stroke depression. Unfortunately, anti-depressants do not improve post-stroke depression until a year after stroke event, and, more importantly, are not as effective in older women as compared to the age-matched men. My study focuses on finding the unique mechanism that possibly underlies post-stroke depression. So far, I have found out that disruption in the brain reward pathway occurs long term after stroke. I am positive that this disruption is tied with the emergence Post Stroke Depression.
Justin Samorajski: MD plus program
Collaborators
Dr. David Earnest: Professor, Neuroscience & Experimental Therapeutics
Alterations of 24-hour or circadian rhythms, in the form of jet lag, shift work and irregular sleep patterns, have been shown to increase the risk for stroke as well as exacerbate stroke severity/recovery. Our studies examine how circadian dysregulation interacts with other non-modifiable risk factors such as biological sex and advancing age to modulate the pathophysiology of ischemic stroke. We are specifically interested in investigating the role of inflammatory signaling via proinflammatory in mediating the pathogenic effects of circadian rhythm dysregulation on ischemic stroke outcomes
Dr. Homa Khosravian: Assistant Professor, Chem Engineering
Dr. Rajesh Miranda: Professor, Neuroscience & Experimental Therapeutics
Dr. Samba Reddy: Professor, Neuroscience & Experimental Therapeutics
Dr. Jun Wang: Assistant Professor, Neuroscience & Experimental Therapeutics
While excessive alcohol consumption is a well-known risk factor for ischemic stroke, how stroke impacts alcohol-associated behavior is unclear. We are interested in exploring how infarction of the dorsolateral versus dorsomedial striatum change alcohol seeking behavior. We are particularly interested in investigating in the aberrant synaptic plasticity of the striato-nigro-striatal circuit in post-stroke alcohol use.