WELCOME TO JAMES HAORAH'S LABORATORY
1. Rat Model of Atherosclerotic Stroke, which is the only long-term survival animal model of intra-cerebral ischemic stroke. We study the mechanisms of alcohol-induced oxidative damage of the arterial vessels, immune cell aggregation, cholesterol accumulation, NLRP3 inflammasome activation, atherosclerotic lesions f and incidence of cerebral ischemic stroke.
2. Animal Model of Thiamine-deficiency diet intake, neuropathy, atrophy and Prevention in chronic alcohol consumption. We study the idea that alcoholics have impaired transport of thiamine (Vita B1) across the intestinal mucosal and brain barrier, thus causes depletion of thiamine in the brain. Our interest is dietary supplement to stabilize thiamine pyrophosphate and pyruvate dehydrogenase for efficient decarboxylation of pyruvate to acetylcoenzyme A.
3. Stabilization of Mitochondrial b-oxidation as Protective Strategy for Oxidative Damage mediated Neurological Disorders. We study the mechanisms of cellular anti-oxidants and oxidants imbalance due to mitochondrial dysfunction in chronic alcohol ingestion. The central idea is that stabilization of β-oxidation by therapeutic agent: 1) replenishes cPT1 and cPT2 functions (mitochondrial membrane function), 2) stabilizes substrates supply for oxidative phosphorylation (mitochondrial inner matrix function), and 3) maintains ATP and antioxidant homeostasis in the matrix. We believe that impairment of this important metabolic pathway is associated with neuroinflammation and neurotoxicity by the formation of fatty acid ethyl esters and activation of phospholipase A2, cyclooxygenase and lipoxygenase in alcoholic CNS.
4. Mice Model of Cerebral Vascular Hemorrhage and Neurotoxicity in Methamphetamine Abuse: We study the mechanisms of METH-induced oxidative injury of BBB, activation of MMP-3/9, VEGF/VEGFR-2 signaling, caspase 1 activation and hemorrhagic stroke. In collaboration with Dr. Gendelman, M.D. Chair of Pharmacology and Experimental Neuroscience, Dr. Haorah is also exploring the idea of preventing HIV-1 transmission and infection in substance of abuse by NanoART. Dr. Haorah’s lab is also actively examining the underlying mechanisms of bio-fuel homeostasis interruption by chronic drug of abuse in the development of neurological disorders.
5. Rat model of primary blast wave traumatic brain injury: We study the idea that primary blast wave: a) causes brain injury due to initial mechanical force leading to molecular and biochemical events, b) causes BBB injury as a key event for neuroinflammation and neuronal loss, c) contributes to cerebrospinal fluid cavitation and BBB/brain injury, and d) substance of abuse worsens the pre-/post- blast simulated pressure wave spectrum on TBI. This is a collaborative project consisting of Dr. Namas Chandra (associate dean, college of engineering, UNL), Dr. Rick Bevins (Chair, dept. of Psychology, UNL). Progress on this joint project is supported by our recent publications and preparation for joint grant application.
6. Prevention of HIV/AIDS progression in substance of abuse by ART and dietary supplements. Substance of abuse, such as alcohol and amphetamine hinders the efficacy of antiretroviral therapy (ART) to control HIV/AIDS progression. Substance of abuse causes oxidative stress, energy depletion, and malnutrition, exacerbating ART toxicity and neuroimmune compromise in malnourished HIV/AIDS subjects. We are studying the idea that suppression of alcohol-induced oxidative stress, neutralization of ART toxicity (Atripla), and restoration of malnutrition and immune function by dietary supplements acetyl-L-carnitine and thiamine can be a gold-standard treatment for prevention of HIV/AIDS progression in alcohol abuse. This joint research collaboration consists of Dr. Haorah, Ph.D. UNMC as principal investigator, Dr. Pankaj Seth, Ph.D, National Brain Research Center, Manesar, Haryana (Govt. of India), and Dr. Matthias Jajo, M.D, Director, Leishiphung Christian Hospital and Research Center, Ukhrul, Manipur India. Currently, 40 malnourished HIV/AIDS subjects are treated with Virotrenz (atripla), acetyl-L-carnitine (ALC), and thiamine (vitamin B1) in Ukhrul district, where 15 % of the population is living with HIV-1 infection.
Alcohol Abuse and Blood-Brain Barrier Dysfunction: Underlying Mechanisms
PI: James Haorah
Source of Funding: NIH/NIAAA (1R21 AA016403-01A2)
Alcohol Abuse and HIV-1 infection: Mechanisms of Combined CNS Injury and Interventions
Multiple PIs: James Haorah and Yuri Persidsky
Source of Funding: NIH/NIAAA (1 R01 AA017398-01)
Neuroprotective mechanisms by astrocytes in alcohol abuse: Therapeutic interventions
PI: James Haorah
Source of Funding: NIH/NIAA (1R21 AA020370-01A1)
- In vitro and animal models for Blood-Brain Barrier
- Biochemistry technologies
- Confocal Imaging facility
- Molecular biology
- Real-time PCR and Western blot analyses
- Real-time transendothelial electrical resistance (TEER) by 1600R ECIS system.
- Radio-labeled tracer molecules
- Detection of fatty acid ethyl esters by GC-MS
- Detection of fatty acids by HPLC
- Detection of fluorescent tracer marker by SpectraMax M5E
Vikas Mishra, PhD
Heather A. Schuetz