Spreading Depolarizations in Brain Trauma and Stroke

Jed Hartings, PhD, leads studies on the clinical significance of spreading depolarizations (SD), a class of pathologic waves that occur in the brain after injury or other insults. SDs are the largest known disturbance of living brain tissue –10X the size of a seizure – and cause disruption at all levels of molecular, cellular, and tissue function. They are now recognized as the central mechanism driving the toxic changes, including neuronal edema and intracellular Ca2+ loading, that lead to tissue death such as infarction after stroke. However, SDs also occur in other conditions of acute injury, including contusion, subdural hematoma, intracerebral hemorrhage, and subarachnoid hemorrhage, and appear to be a requisite mechanism of tissue damage across these conditions.

SDs are studied in patients by placing electrode strips on the brain when patients require neurosurgery. By recording brain activity for several days in the intensive care unit, we find that 60% of patients exhibit SDs after brain trauma, and often these waves recur in a continuous, repetitive pattern for days. In some cases, this causes the progressive deterioration of brain activity to the point of isoelectricity (flat-line). In several large multicenter cohort studies, we have found that a severe course of SDs is an independent predictor of worse patient outcomes. These results raise the possibility that monitoring and treatment of SDs in the clinic could be an effective strategy to improve outcomes –survival and recovery– from severe brain trauma.

We are now testing this idea in a multicenter, randomized clinical trial, using a combination of physiologic and pharmacologic (ketamine) therapies to prevent and treat SDs in real time in the neuroscience intensive care unit. It is possible that, as both a marker and mechanism of progressive brain damage, the monitoring of SDs could become a new cornerstone for managing and treating acute brain injury. To advance clinical adoption, we are also developing custom software and algorithms to facilitate SD monitoring. The automated software solutions are expected to accelerate and standardize the display, recognition, and quantitative assessment of SDs in brain wave recordings, making it easier for physicians to apply this new science in their practices.

Our group collaborates widely with other investigators at UC, and also internationally with other medical centers in the Co-Operative Studies on Brain Injury Depolarization (COSBID), in both laboratory and clinical research.

Resources and Links

• Co-Operative Studies on Brain Injury Depolarization
• Brain Tsunamis
• Documentary Film: COSBID and the Clinical Discovery of Spreading Depolarizations  

News and Media

Tedeschi T. Study: Machine Learning Aids in Detection of 'Brain Tsunamis.' UC News, March 9, 2025.

WVXU, Ann Thompson reporting, June 12, 2023: "After head trauma, heart attack or stroke, brain cells can continue dying for weeks. UC researchers have a possible prevention plan."

Smith, David W. When Heads Come Together: Discovering Nature's Secrets for Preventing Traumatic Brain Injury. FittingWords, LLC, 2023, pp. 155-162, 177-179.

Forbes, J. First-of-its-kind trial hopes to minimize the effects of brain injury. UC News, February 3,2022.

Collins, TR. Spreading depolarizations are brain injury's "silent culprit," expert says. Neurology Today, July 25, 2019

The Dana Foundation, “The End Comes as a Wave”. Sophie Fessl, Sept 26, 2018.

Kate Sheridan. Does a dying brain mean death? Some cellular changes may be reversible, new evidence shows. Newsweek February 27, 2018.

WVXU, Ann Thompson reporting, March 12, 2018: “The sounds inside your brain right before death.”

Mayfield Clinic Short Film, “Research – In the Long Run” 

“Watch Out for That Brain Tsunami”, M.J. Gertner, The Atlantic

Selected Publications

Sword JJ, Sparks T, Debs LH, et al. Acute-phase recording of the spreading depolarization continuum in aged nonhuman primates during focal ischemic stroke. Stroke 2025; 5694): 974-986.

Hartings JA, Dreier JP, Ngwenya LB, et al. Improving neurotrauma by depolarization inhibition with combination therapy: a phase 2 randomized feasibility trial. Neurosurgery 2023; 93(4): 924-931.

Horst V, Kola V, Lemale CL, et al. Spreading depolarization and angiographic spasm are separate mediators of delayed infarcts. Brain Communication 2023; 5(2): facd080.

Hartings JA, Andaluz N, Bullock MR, et al. Prognostic value of spreading depolarizations in patients with severe traumatic brain injury. Jama Neurology 2020; 77(4):489-499.

Dreier JP, Major S, Foreman B, et al. Terminal spreading depolarization and electrical silence in death of human cerebral cortex. Ann Neurol 2018; 83:295-310.1.      

Hartings JA. Spreading depolarization monitoring in neurocritical care of acute brain injury. Curr Opin Crit Care 2017; 23:94-102.

Hartings JA, York J, Carroll CP, et al. Subarachnoid blood acutely induces spreading depolarizations and early cortical infarction. Brain 2017; 140:2673-90.

Hinzman JM, DiNapoli VA, Mahoney EJ, Gerhardt GA, Hartings JA. Spreading depolarizations mediate excitotoxicity in the development of acute cortical lesions. Exp Neurol 2015.

Hartings JA, Shuttleworth CW, Kirov SA, et al. The continuum of spreading depolarizations in acute cortical lesion development: Examining Leao's legacy. J Cereb Blood Flow Metab 2017; 37:1571-94.

Dreier JP, Fabricius M, Ayata C, et al. Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group. J Cereb Blood Flow Metab 2017; 37:1595-625.

Hartings JA, Wilson JA, Hinzman JM, et al. Spreading depression in continuous electroencephalography of brain trauma. Ann Neurol 2014; 76:681-94.

Hartings JA, Bullock MR, Okonkwo DO, et al. Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study. Lancet Neurol 2011; 10:1058-64.