Hemispheric asymmetries in rodent models of neurological diseases: a systematic review.

Introduction: Hemispheric asymmetries are a core organizational principle of the vertebrate brain, but they are still not fully integrated into the study of preclinical models of neurological disease. Although many rodent models naturally include lateralization through unilateral interventions, hemispheric differences are not consistently examined or systematically reported. Methods: A systematic review was conducted following PRISMA guidelines, combining evidence from 48 studies on hemispheric asymmetries in rodent models of neurological conditions, including mild traumatic brain injury, epilepsy, stroke, Alzheimer's, and Parkinson's disease. Results: Across these models, disease processes cause strong lateralized effects on behavior, neurochemistry, and regional metabolism. In epilepsy models specifically, hemispheric asymmetries depend on the model: early seizure spread and network excitability can be lateralized, while other paradigms show more symmetric responses, emphasizing the role of baseline circuit asymmetries and genetic background. Similar lateralized effects are seen in stroke and Parkinson's models, reflecting clinical phenomena such as lesion-side-dependent outcomes and unilateral symptom onset. Discussion: Models focusing on intrinsic hemispheric asymmetry or interhemispheric/bilateral response highlight existing differential sensitivity to experimental manipulations that may predispose the system to asymmetric outcomes. Nonetheless, variability and dynamic shifts in hemispheric organization are rarely taken into account. Incorporating hemispheric analysis systematically into experimental design and data interpretation could enhance the sensitivity, clarity, and clinical relevance of rodent models of neurological disease.