Senior Research Technician

July 2008-February 2012

Ms. Mitchell started in the Kraig Lab in March 2008 to complete a month-long undergraduate internship via the Cornell College Dimensions Program.  After receiving her B.A. in Biology in May 2008 from Cornell College, Ms. Mitchell began working full-time in the Kraig Lab.  Ms. Mitchell’s past research investigated the underlying immune signaling of tumor necrosis factor-alpha (TNF-α) and interleukin-11 (IL-11) in cold-preconditioning neuroprotection before the onset of disease.  TNF-α and IL-11 have previously been implicated as pro- and anti-inflammatory cytokines in disease; however, administering cold-preconditioning before the onset of brain injury reversed the roles of these cytokines and revealed that abrogation of IL-11 doubled the degree of preconditioning neuroprotection. 

This finding led to newly focused research involving neuronal activity-dependent signaling of cytokines, especially IL-11.  Preconditioning from environmental enrichment not only initiates neuroprotection and increased myelination involving IL-11, but also prevents the hyperexcitability of brain needed to initiate spreading depression, the likely cause of migraine and demyelination in susceptible brain.

Peer-Reviewed Publications

Kraig, R. P., Mitchell, H. M., Christie-Pope, B., Kunkler, P. E., White, D. M., Tang, Y. P. and Langan, G. (2010) TNF-alpha and microglial hormetic involvement in neurological health & migraine. Dose Response, 8, 389-413. 

Mitchell, H. M., White, D. M. and Kraig, R. P. (2010) Strategies for study of neuroprotection from cold-preconditioning. J Vis Exp.

Mitchell, H. M., White, D. M., Domowicz, M. S. and Kraig, R. P. (2011) Cold pre-conditioning neuroprotection depends on TNF-alpha and is enhanced by blockade of interleukin-11. J Neurochem, 117, 187-196.

Pusic, A. D., Grinberg, Y. Y., Mitchell, H. M. and Kraig, R. P. (2011) Modeling neural immune signaling of episodic and chronic migraine using spreading depression in vitro. J Vis Exp.

Abstracts

Kraig RP, White DM, Mitchell HM (2008).  TNF-α drives cold-preconditioning neuroprotection and reprogramming of inflammatory cytokine cascade reactions.  Soc Neurosci 34:  Prog #151.9

Mitchell HM, White DM, Kraig RP (2009) Cold-preconditioning neuroprotection of hippocampus follows a hormetic dose-response pattern initiated by tumor necrosis factor-α from microglia and potentially evoked by adaptive interleukin-11 signaling from neurons.  Soc Neurosci 35:  Prog #744.4

Mitchell HM, Levasseur V, Kraig RP (2010) TNF-α increases spreading depression susceptibility via reduced GABAergic inhibition—implications for the transformation of episodic to chronic migraine.  Soc Neurosci 36:  Prog #346.3

Mitchell HM, Pusic AD, Kraig RP (2011) Interleukin-11 mitigates spreading depression susceptibility:  implications for migraine.  Soc Neurosci 37: Prog #875.22.

Pusic AD, Mitchell HM, Kraig RP (2011) IFN-γ from T-cells modulates susceptibility to- and transient myelination from – spreading depression:  implications for migraine therapy.  Soc Neurosci 37: Prog #875.16.