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Updated: Jun 16, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Administration of ketogenic intervention as a potential treatment during post-traumatic brain injury recovery: a
Daaniyal Y Quddus1, Serhat Aydin1, Ayesha Akbar Waheed1
1Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Background:
Traumatic brain injury (TBI) affects 69 million individuals annually and represents a major global health burden. Ketogenic interventions have emerged as a potential therapy to address deficits following TBI. This scoping review updates previous work to synthesize evidence on ketogenic therapies for TBI, examining mechanistic insights, clinical feasibility, and barriers.
Methods:
A systematic search was conducted following the methodological framework of Arksey and O'Malley (2005) and JBI guidance. Findings are reported in accordance with PRISMA 2020 guidelines complemented by the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Studies were included if they used TBI models in human or animal subjects; investigated ketogenic interventions; reported quantitative clinical, functional, or metabolic outcomes; and enrolled more than five participants in clinical trials. Studies were excluded if they were conducted in vitro, did not involve TBI or ketogenic interventions, were not original research, were duplicate publications, or lacked English full text manuscripts.
Results:
Out of 421 studies screened, 32 studies met the inclusion criteria. 25 animal studies and 7 human studies were analyzed. 68.0% of animal studies used exclusively male specimens. The total pooled male-to-female ratio across human studies was 53:24, reflecting an approximately twofold predominance of male participants. Studies were evaluated using clusters of the most-assessed frameworks. Animal investigations evaluated metabolic pathways in 23 out of 25 (92.0%) studies, neuroprotective effects in 15 out of 25 (60.0%) studies, and behavioral assays in 13 out of 25 (52.0%) studies. Human studies assessed feasibility in 7 out of 7 (100%) studies, safety in 5 out of 7 (83.33%) studies, and efficacy in 4 out of 7 (66.67%) studies. Clinical trials consistently demonstrated feasibility in monitored settings.
Conclusion:
Ketogenic interventions improve metabolic dysfunction in preclinical models with variable neuroprotective and functional effects. Clinical evidence demonstrates feasibility but lacks adequately powered efficacy trials. Larger controlled trials with standardized endpoints with balanced age and sex representation are needed to determine efficacy.
