The Weil Lab at The Ohio State University Wexner Medical Center is focused on understanding the basic biology and long-term consequences of traumatic brain injuries.
Traumatic brain injury (TBI) is a serious public health issue costing Americans over 75 billion dollars annually in healthcare costs and lost productivity. One prominent feature of TBI is that injuries make future injuries more likely and more devastating. Our lab is interested in understanding the molecular and biochemical basis of this phenomenon. Being part of the neurological institute has enabled interdisciplinary collaboration with physicians and researchers dedicated to improving the lives of patients with TBI.
Zachary Weil, PhD
Assistant Professor, Department of Neuroscience; Laboratory Director
The Weil Laboratory focuses on understanding the basic biology and long-term consequences of traumatic brain injuries (TBI). They study the molecular and biochemical basis of why TBIs make future injuries more likely and more devastating. Dr. Weil is interested in how environmental and temporal variables can interact with the immune, autonomic and neuroendocrine systems to control physiology and behavior. He is also interested in understanding how environmental variables can render organisms differentially susceptible to nervous system injuries.
Undergraduate Student Assistant
Undergraduate Student Assistant
Kate Karelina, PhD
Undergraduate Student Assistant
Undergraduate Student Assistant
Undergraduate Student Assistant
Undergraduate Student Assistant
Long Term Consequences of Early Brain Injuries
Metabolic Effects of Concussion
The pathophysiology of traumatic brain injury (TBI) is complex but involves diffuse axonal injury, frank neuronal death, inflammation and persistent metabolic abnormalities. There is a consistent phenomenon across brain injury subtypes that the capacity for the brain to utilize energy (viz. glucose) is significantly modulated following injury. Most studies have reported a transient period of hypermetabolism followed by a prolonged hypometabolic phenotype. This phenomenon has been reported in both animal and human studies. The initial hypermetabolism is apparently the response to the release of excitatory amino acids immediately following injury and may be necessary to recover some aspects of homeostasis in the injured brain. The recovery of cognitive and executive function correlates strongly with the return of normal glucose metabolism in both humans and animals. However, no studies have definitively linked alterations in glucose metabolism to either cognitive/executive function or vulnerability to subsequent injury.
The insulin receptor system is a prime target for TBI treatment as it has potent neuroprotective actions in the acutely injured brain and in chronic neurodegenerative states (CNS). Insulin insensitivity in the periphery is known as type 2 diabetes, but there is mounting evidence that central insulin resistance is a key component of neurodegenerative (Alzheimer’s in particular) and metabolic disease. The most fundamental link between CNS pathology and insulin insensitivity is inflammation, and in particular tumor necrosis factor (TNF), which rapidly reduces insulin signaling in part by activating signaling pathways that phosphorylate and inactivate the insulin-receptor substrate protein (IRS-1), thereby preventing insulin signaling. Our lab is currently investigating the role of these phenomena in repeated TBI.
McCartney H., Johnson A.D., Weil Z.M., and Givens, B. (2004). Theta reset produces optimal conditions for long-term potentiation. Hippocampus, 14:684-687.
Pyter L.M., Weil Z.M., and Nelson R.J. (2005). Latitude affects photoperiod-induced changes in immune response in meadow voles (Microtus pennsylvanicus). Canadian Journal of Zoology, 83:1271–1278.
Weil Z.M., Bowers S.L., Pyter L.M., and Nelson R.J. (2006). Social interactions alter proinflammatory cytokine gene expression and behavior following endotoxin administration. Brain, Behavior, and Immunity, 20:72-79.
Weil Z.M., Hotchkiss A.K., Gatien M.L., Pieke-Dahl S., and Nelson R.J. (2006). Melatonin receptor (MT1) knockout mice display depression-like behaviors and deficits in sensorimotor gating. Brain Research Bulletin, 68:425–429.
Benderlioglu Z., Eish J., Weil Z.M., and Nelson R.J. (2006). Low temperatures during early development influence subsequent maternal and reproductive function in adult female mice. Physiology & Behavior, 87:416–423.
Huang A.S., Beigneux A., Weil Z.M., Kim P.M., Molliver M.E., Blackshaw S., Young S.G., Nelson R.J., and Snyder S.H. (2006). D-Aspartate regulates melanocortin formation and function: behavioral alterations in D-aspartate oxidase deleted mice. The Journal of Neuroscience, 26:2814-2819.
Weil Z.M., Bowers S.L., Dow E.R., and Nelson R.J. (2006). Maternal aggression persists following lipopolysaccharide-induced activation of the immune system. Physiology and Behavior, 87:694-699.
Weil Z.M., Pyter L.M., Martin II L.B., and Nelson R.J. (2006). Early-life photoperiods organize adult immune responses in Siberian hamsters (Phodopus sungorus). American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 290: R1714-R1719.
Weil Z.M., Huang A.S., Beigneux A., Kim P.M., Molliver M.E., Blackshaw S., Young S.G., Nelson R.J., and Snyder S.H. (2006). Behavioural alterations in male mice lacking the gene for D-aspartate oxidase. Behavioural Brain Research, 171:295-302.
Martin II L.B., Weil Z.M., Kuhlman J.R., and Nelson R.J. (2006). Trade-offs between cutaneous immune responses in female white-footed mice (Peromyscus leucopus). Functional Ecology, 20: 630-636.
Weil Z.M., Martin II L.B., and Nelson R.J. (2006). Photoperiod differentially affects immune function and reproduction in collared lemmings (Dicrostonyx groenlandicus). Journal of Biological Rhythms, 21:384-393.
Weil Z.M., Martin II L.B., Workman J.L., and Nelson R.J. (2006). Immune challenge retards seasonal reproductive regression: evidence for terminal investment. Biology Letters, 2:393-386.
Martin II L.B., Weil Z.M., and Nelson R.J. (2006). Refining approaches and diversifying directions in ecoimmunology. Integrative and Comparative Biology, 46:1030-1039.
Martin II L.B., Navara K.J., Weil Z.M., and Nelson R.J. (2007). Maintenance of immunological memory is compromised by food restriction in male deer mice, Peromyscus maniculatus. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 290: R316-R320.
Weil Z.M., Kidder S.L., and Nelson R.J. (2007). Photoperiod alters affective responses in collared lemmings. Behavioural Brain Research, 179: 305-309.
Weil Z.M., Workman J.L., and Nelson R.J. (2007). Housing condition alters immunological and reproductive responses to day length in Siberian hamsters (Phodopus sungorus). Hormones and Behavior, 52: 261-266.
Martin II L.B., Weil Z.M., and Nelson, R.J. (2007). Immune defense and reproductive pace of life in deer mice. Ecology, 88:2516-2528.
Martin II L.B., Weil Z.M., and Nelson R.J. (2008). Seasonal changes in vertebrate immune activity: mediation by physiological trade-offs. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 363: 321–339.
Martin II L.B., Weil Z.M., and Nelson R.J. (2008). Fever and sickness behavior vary among congeneric rodents. Functional Ecology, 22: 68-77.
Workman J.L., Weil Z.M., Tuthill C.R., and Nelson R.J. (2008). Maternal pinealectomy increases depressive-like responses in Siberian hamster offspring. Behavioural Brain Research, 189: 387-391.
Martin II L.B., Weil Z.M., Bowers S.L., and Nelson R.J. (2008). Sex-specific effects of glucose deprivation on immunity and reproduction in Siberian hamsters (Phodopus sungorus). Journal of Comparative Physiology B, 178: 623-628.
Weil Z.M., Norman G., DeVries A.C., and Nelson R.J. (2008). The injured nervous system: A Darwinian perspective. Progress in Neurobiology, 86: 48-59.
Weil Z.M., Norman G., Barker J.M., Su A.J., Nelson R.J., and DeVries A.C. (2008). Social isolation potentiates cell death and inflammatory responses after global ischemia. Molecular Psychiatry, 13:913-915.
Weil Z.M., Gatien-Hotchkiss M.L., and Nelson R.J. (2008). Photoperiod alters pain responsiveness via changes in pelage characteristics. The Canadian Journal of Zoology, 86:1212-1216.
Weil Z.M., Norman G., DeVries A. C., Berntson G.G., and Nelson R.J. (2009). Photoperiod alters autonomic regulation of the heart. Proceedings of the National Academy of Sciences: 106:4525-4530.
Weil Z.M., Norman G., Karelina K., Morris J., Barker J.M., Su, A.J., Walton J.C., Bohinc S., Nelson R.J., and DeVries A.C. (2009). Sleep deprivation attenuates inflammatory responses and ischemic cell death. Experimental Neurology: 218:129-136.
Fonken K.L., Finy S.M., Walton J.C., Weil Z.M., Workman J.L., Ross J., and Nelson R.J. (2009). Influence of light at night on murine anxiety- and depressive-like responses. Behavioural Brain Research: 205:349-354.
Weil Z.M., Karelina K., Su A.J., Barker J.M., Norman G.J., Zhang N., DeVries A.C., and Nelson R.J. (2009). Time-of-day determines neuronal damage and mortality after cardiac arrest. Neurobiology of Disease: 36:352-360.
Weil Z.M., Zhang Q., Hornung A., Blizard D., and Pfaff D.W. (2010). Impact of generalized brain arousal on sexual behavior. Proceedings of the National Academy of Sciences: 107:2265-2270.
Bailey M.T., Walton J.C., Dowd S.E., Weil Z.M., and Nelson R.J. (2010). Photoperiod modulates gut bacteria composition. Brain, Behavior and Immunity: 24:577-584.
Karatsoreos I.N., Bhagat S.M., Weil Z.M., Pfaff D.W., and McEwen B.S. (2010). Chronic corticosterone treatment results in physiological and behavioral changes mimicking the metabolic syndrome. Endocrinology: 151:2117-2127.
Weil Z.M., Murakami G., and Pfaff D.W. (2010). Reproductive behaviors: New developments in concepts and in molecular mechanisms. Progress in Brain Research. Progress in Brain Research: 181:35-41.
Karelina K., Walton J.C., Weil Z.M., Norman G., Nelson R.J., and Devries A.C. (2010). Estrous phase alters social behavior in a polygynous but not a monogamous Peromyscus species. Hormones and Behavior: 58:193-199.
Gagnidze K., Weil Z.M., and Pfaff D.W. (2010). Histone modifications proposed to regulate sexual differentiation of brain and behavior. Bioessays: 32:932-939.
Fonken L.K., Workman J.L., Walton J.C., Weil Z.M., Morris, J.S., Haim, A. and Nelson R.J. (2010). Light at night increases body mass by shifting the time of food intake. Proceedings of the National Academy of Sciences: 107:18664-9.
Walton J.C., Chen Z., Weil Z.M., Pyter L.M., Travers J.B., and Nelson R.J. (2011) Photoperiod-mediated impairment of long term potentiation and learning and memory in male white-footed mice. Neuroscience: 175:127-132.
Weil Z.M., Workman J.L., Karelina K., and Nelson R.J. (2011). Short photoperiods alter cannabinoid receptor expression in hypothalamic nuclei related to energy balance. Neuroscience Letters: 491:99-103.
Norman G.J., Morris J., Karelina K., Weil Z.M., Zhang N., Al-Abed Y., Brothers H., Wenk G., Pavlov V., Tracey K., and DeVries A.C. (2011). Cardiopulmonary arrest and resuscitation disrupts cholinergic anti-inflammatory processes: a role for cholinergic α7 nicotinic receptors. The Journal of Neuroscience 31:3446-3452.
Schober J., Weil Z.M., and Pfaff D.W. (2011). How generalized CNS arousal strengthens sexual arousal (and vice versa). Hormones and Behavior. 59:689-695.
Walton J.C., Weil Z.M., and Nelson R.J. (2011). Influence of photoperiod on hormones, behavior, and immune function. Frontiers in Neuroendocrinology 32:303-319.
Bedrosian T.A., Herring K., Weil Z.M., and Nelson R.J. (2011). Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice. Proceedings of the National Academy of Sciences. 108:11686-11691.
Quinkert A., Vimal V., Weil Z.M., Reeke G., Schiff N., Banavar J., and Pfaff D.W. (2011). Quantitative descriptions of generalized arousal, an elementary function of the vertebrate brain. Proceedings of the National Academy of Sciences. 108:15617-15623.
Fonken L.K., Xu X., Weil Z.M., Chen G., Sun Q., Rajagopalan S., and Nelson R.J. (2011). Inhalation of fine particulates alters hippocampal neuronal morphology. Molecular Psychiatry. 16:973.
Fonken L.K., Xu X., Weil Z.M., Chen G., Sun Q., Rajagopalan S., and Nelson R.J. (2011). Air pollution impairs cognition, provokes depressive-like behaviors, and alters hippocampal cytokine expression and morphology. Molecular Psychiatry. 16:987-995.
Fonken L.K., Bedrosian T.A., Michaels H., Weil Z.M., and Nelson R.J. (2012). Short photoperiods attenuate central responses to an inflammogen. Brain Behavior and Immune Function. 26:617-622.
Walton J. C., Grier A.J., Weil Z.M., and Nelson R.J. (2012). Photoperiod and stress regulation of corticosteroid receptor, brain derived neurotrophic factor, and glucose transporter GLUT3 mRNA in the hippocampus of Siberian hamsters (Phodopus sungorus). Neuroscience. 213:106-111.
Ashley N.T, Zhang N., Weil Z.M., Magalang U., and Nelson R.J. (2012). Photoperiod alters duration and intensity of non-REM sleep following immune challenge in Siberian hamsters (Phodopus sungorus). Chronobiology International. 29:683-692.
Walton J.C., Pyter L.M., Weil Z.M., and Nelson R.J. (2012). Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus). PLOS One. 7: e42743.
Weil Z.M. (2012). Ischemia-induced hyperglycemia: consequences, neuroendocrine regulation, and a role for RAGE. Hormones and Behavior. 62:280-285.
Bedrosian T.A., Weil Z.M., and Nelson R.J. (2012). Chronic citalopram improves depressive behaviors associated with light at night. Behavioral Neuroscience, 126:654-658.
Ashley N.T., Weil Z.M., and Nelson R.J. (2012). Inflammation: mechanisms, costs, and natural variation. Annual Review of Ecology, Evolution, and Systematics. 43:385-406.
McCall T., Weil Z.M., Nacher J., Bloss E.B., El Maarouf A., Rutishauser U., and McEwen B.S. (2013). Depletion of polysialic acid from neural cell adhesion molecule (PSA-NCAM) increases CA3 dendritic arborization and alters behavioral and molecular responses to chronic stress. Experimental Neurology 24:5-12.
Bedrosian T.A., Herring K.L., Walton J.C., Fonken L.K., Weil Z.M., and Nelson R.J. (2013) Evidence for feedback control of pineal melatonin secretion. Neuroscience Letters 542:123-125.
Bedrosian T.A., Galan A., Vaughn C.A., Weil Z.M., and Nelson R.J. (2013). Light at night alters daily patterns of cortisol and clock proteins in female Siberian hamsters. Journal of Neuroendocrinology 25:590-596.
Ashley N.T., Walton J.C., Haim A., Zhang N., Prince L.A., Fruchey A.M., Lieberman R.A., Weil Z.M., Magalang U.J., and Nelson R.J. (2013). Sleep deprivation reduces peripheral and hypothalamic IL-1 gene expression independent of photoperiod and circulating cortisol in endotoxin-challenged male Siberian hamsters (Phodopus sungorus). Journal of Experimental Biology. 216:2581-2586.
Bedrosian T.A., Vaughn C.A., Galan A. Daye G., Weil Z.M., and Nelson R.J. (2013). Nocturnal light exposure impairs affective responses in a wavelength-dependent manner. Journal of Neuroscience 33:13081-13087.
Aubrecht G.T., Weil Z.M., Magalang U., and Nelson R.J. (2013). Dim light at night interacts with intermittent hypoxia to alter cognitive and affective responses. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 305:R78-86.
Fonken L.K., Weil Z.M., and Nelson R.J. (2013). Dark nights reverse metabolic disruption caused by dim light at night. Obesity 21:1159-1164.
Borniger J.C., Weil Z.M., Zhang N., Nelson R.J. (2013). Dim Light at Night does not Disrupt Timing or Quality of Sleep in Mice. Chronobiology International 30:1016-1023.
Fonken L.K., Aubrecht T.G., Meléndez-Fernández O.H., Weil Z.M., and Nelson R.J. (2013). Dim light at night disrupts molecular circadian rhythms and increases body weight. Journal of Biological Rhythms 28:262-271.
Bedrosian T.A., Weil Z.M., and Nelson R.J. (2013). Chronic dim light at night provokes reversible depression-like phenotype: possible role for TNF. Molecular Psychiatry 18:93-936.
Fonken L.K., Lieberman, R.A., Weil Z.M., and Nelson R.J. (2013). Dim light at night exaggerates weight gain and inflammation associated with a high fat diet in male mice. Endocrinology 21:1159-1164.
Morris J.S., Weil Z.M., and Nelson R.J. (2013). Sexual experience and testosterone during adolescence alters adult neuronal morphology and behavior. Hormones and Behavior. 64:454-460.
Gagnidze K., Weil Z.M., Faustino L.C., Schaafsma S.M., and Pfaff D.W. (2013). Early chromatin modifications in ventromedial hypothalamic and preoptic cells following estradiol administration. Journal of Neuroendocrinology. 25:939-955.
Walton J.C., Selvakumar B., Weil Z.M., Snyder S.H., and Nelson R.J. (2013). Neuronal nitric oxide synthase and NADPH oxidase interact to affect cognitive, affective, and social behaviors in mice. Behavioural Brain Research. 256:320-327.
Fonken L.K., Weil Z.M., and Nelson R.J. (2013). Mice exposed to dim light at night exaggerate inflammatory responses to lipopolysaccharide. Brain, Behavior and Immunity 34:159-163.
Ikeno T., Weil Z.M., and Nelson R.J. (2013). Photoperiod affects the diurnal rhythm of hippocampal neuronal morphology of Siberian hamsters. Chronobiology International. 30:1089-1100.
Bedrosian T.A., Aubrecht T.G., Kaugars K.E., Weil Z.M., and Nelson R.J. (2013). Artificial light at night alters delayed-type hypersensitivity reaction in response to acute stress in Siberian hamsters. Brain, Behavior and Immune Function. 34:39-42.
Zhang Y., Guan Z., Reader B., Shawler T., Mandrekar-Colucci S., Huang K., Weil Z.M., Bratasz A., Wells J., Powell N.D., Sheridan J.F., Whitacre C.C., Rabchevsky A.G., Nash M.S., and Popovich P.G. (2013). Autonomic dysreflexia causes chronic immune suppression after spinal cord injury. Journal of Neuroscience. 33:12970-12981.
Bedrosian T.A., Vaughn C.A., Weil Z.M., and Nelson R.J. (2013). Behavioral of laboratory mice is altered by light pollution within the housing environment. Animal Welfare. 22:783-787.
Fonken L.K., Melendez-Fernandez O.H., Weil Z.M., and Nelson R.J. (2014). Exercise attenuates the metabolic effects of dim light at night. Physiology and Behavior. 124:33-36.
Morris J.S., Weil Z.M., and Nelson R.J. (2014). Early Sexual Experience Alters Voluntary Alcohol Intake in Adulthood. Neuroscience Letters. 563:129-133.
Aubrecht T.G., Weil Z.M., and Nelson R.J. (2014). Melatonin treatment during early life interacts with stress to alter neuronal morphology and provoke depressive-like responses. Behavioral Brain Research. 263:90-97.
Ikeno T., Weil Z.M., and Nelson R.J. (2014). Dim light at night disrupts the short-day response in Siberian hamsters. General and Comparative Endocrinology. 197:56-64.
Ikeno T., Weil Z.M., and Nelson R.J. (2014). Timing of light pulses and photoperiod on the diurnal rhythms of hippocampal neuronal morphology of Siberian hamsters. Neuroscience. 270:69-75.
Weil Z.M., and Nelson R.J. (2014). Introduction to the Special Issue on “Circadian Rhythms in Behavioral Neuroscience”. Behavioral Neuroscience.128:237-239.
Walton, J.C., Aubrecht, T.G., Weil, Z.M., Leuner, B., Nelson, R.J. (2014). Photoperiodic regulation of hippocampal neurogenesis in adult male white-footed mice (Peromyscus leucopus). European Journal of Neuroscience. 40:2674-2679.
Weil Z.M., Gaier K.R., Karelina K. (2014). Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury. Neurobiology of Disease. 70:108-116.
Aubrecht T.G., Weil Z.M., Ariza M.E., Williams M., Glaser R., Reader B., Sheridan J., and Nelson R.J. (2014). Epstein-Barr virus (EBV)-encoded dUTPase and chronic restraint induce impaired learning and memory and sickness responses. Physiology and Behavior. 137:18-24.
Aubrecht T.G., Weil Z.M., and Nelson R.J. (2014). Dim light at night interferes with the development of the short day phenotype and impairs cell-mediated immunity in Siberian hamsters (Phodopus sungorus). Journal of Experimental Zoology Part A. 321(8):450-456.
Weil Z.M., Borniger J.C., Cisse Y.M., Abi Salloum B.A., and Nelson R.J. (2015). Neuroendocrine control of photoperiodic changes in immune function. Frontiers in Neuroendocrinology. 37: 108-118.
Weil ZM, Karelina K, Gaier KR, Corrigan TED & Corrigan J, 2016. Juvenile traumatic brain injury increases alcohol consumption and reward in female mice. Journal of Neurotrauma, 33(9): 895-903.
Karelina K. and Weil Z.M. (in press). Neuroenergetics of traumatic brain injury. Concussion Journal. doi: 10.1089/neu.2015.3953.
Weil ZM, Corrigan JD & Karelina K, 2016. Alcohol abuse after traumatic brain injury: experimental and clinical evidence. Neuroscience and Biobehavioral Reviews, 62: 89-99.
Karelina K, Sarac B, Freeman L, Gaier KR and Weil ZM, 2016. Traumatic brain injury and obesity induce persistent central insulin resistance. European Journal of Neuroscience, 43(8): 1034-1043.
Weil ZM & Karelina K, 2017. Traumatic brain injuries during development: implications for alcohol abuse. Frontiers in Behavioral Neuroscience, 11:135. doi: 10.3389/fnbeh.2017.00135
Karelina K, Gaier KR, Prabhu M, Wenger V, Corrigan TED & Weil ZM, 2017. Binge ethanol in adulthood exacerbates negative outcomes following juvenile traumatic brain injury. Brain, Behavior and Immunity, 60: 304-311.