Helen M. Bramlett, Ph.D.

The Pathophysiology and Treatment of CNS Injury

My research spans neurotrauma, neurodegeneration, ischemia, and spinal cord injury, with major thematic strengths in inflammasome biology, sex‑ and age‑dependent vulnerability, therapeutic hypothermia, extracellular vesicle therapies, neuroprotective molecules, and transcriptomic/proteomic characterization of injury responses.

A substantial portion of my collaborative work defines how inflammasome signaling contributes to secondary injury mechanisms in TBI, stroke, Alzheimer’s disease (AD), neurodevelopmental injury, and gut–brain axis disruption. These studies demonstrated region‑specific inflammasome protein expression, genetic modulation of pyroptosis pathways (e.g., GSDMD knockout), and how peripheral factor such as stool‑derived extracellular vesicle amplify CNS inflammation after TBI and stroke, including in AD‑transgenic mice.

Our group has made multiple advances in cell‑ and vesicle‑based therapies for neurotrauma, showing that human Schwann cell‑derived exosomes and neural stem cells mitigate microglial activation, histopathology, and behavioral deficits after penetrating or blunt brain injury. Similar work examines biomarker responses and injury severity correlations in acute traumatic spinal cord injury.

We have also contributed extensively to investigations of therapeutic hypothermia and temperature modulation, including novel approaches using nanovanilloid‑mediated targeted cooling and single‑cell RNA sequencing to map cell‑type‑specific hypothermia responses after TBI.

A strong mechanistic theme in my research involves hormonal, metabolic, and sex‑dependent influences on CNS injury. These studies show how menopause‑associated frailty, estrogen receptor‑β signaling, nicotine/contraceptive interactions, and electronic cigarette vapor exposure alter ischemic outcome, neuronal survival, inflammatory signaling, and behavioral recovery, often with marked female-specific vulnerabilities.

Our work on ischemia includes discoveries that recombinant irisin and whole‑body vibration therapy can induce transcriptomic profiles associated with neuroprotection and ischemic tolerance in middle‑aged or reproductively senescent animals. Complementary studies identify interactions between metabolic hormones (e.g., osteocalcin) and brain senescence.

Another major emphasis is systems-level characterization of CNS injury. We have led or contributed to multimodal MRI, neuroproteomics, machine learning–based recovery prediction, and circulating biomarker analyses across models of TBI and SCI. These studies reveal longitudinal patterns of structural change, electrophysiological abnormalities, and predictive biomarker signatures linked to injury severity and outcome.

Finally, our research extends into bone biology after spinal cord injury, demonstrating how low‑intensity vibration and RANKL inhibition reduce immobilization‑induced bone loss, broadening the translational relevance beyond CNS tissue.