A New Model for Diffuse Brain Injury by Rotational Acceleration: I. Model, Gross Appearance, and Astrocytosis

Abstract

Rapid head rotation is a major cause of brain damage in automobile crashes and falls. This report details a new model for rotational acceleration about the center of mass of the rabbit head. This allows the study of brain injury without translational acceleration of the head. Impact from a pneumatic cylinder was transferred to the skull surface to cause a half-sine peak acceleration of 2.1 x 10(5) rad/s2 and 0.96-ms pulse duration. Extensive subarachnoid hemorrhages and small focal bleedings were observed in the brain tissue. A pronounced reactive astrogliosis was found 8-14 days after trauma, both as networks around the focal hemorrhages and more diffusely in several brain regions. Astrocytosis was prominent in the gray matter of the cerebral cortex, layers II-V, and in the granule cell layer and around the axons of the pyramidal neurons in the hippocampus. The nuclei of cranial nerves, such as the hypoglossal and facial nerves, also showed intense astrocytosis. The new model allows study of brain injuries from head rotation in the absence of translational influences.

Therapy Development for Diffuse Axonal Injury

“…More recently, additional gyrencephalic animal models of DAI have been developed, such as captive bolt head impact in sheep and pigs and head rotational acceleration in neonatal pigs and adult rabbits. [65][66][67][68] For evaluation of emerging therapies for DAI, the large animal studies benefit from their close relation to the human brain. They suffer from limitations for determining mechanisms of action, functional analyses, and number of subjects achievable for each experimental group, however.…”

Modelos experimentales de traumatismo craneoencefálico

“…Por lo tanto, los modelos de daño por aceleración son más fáciles de desarrollar en animales con una cabeza de mayor tamaño, como son los monos y cerdos 42,80 . Sin embargo, debido al alto coste y más difícil manejo de estos animales, se han desarrollado en la última década modelos de daño difuso en roedores 20,21,47,73 . El inconveniente de los modelos de daño difuso en roedores es que debido a la gran fuerza que es necesario aplicar sobre el cráneo para generar la aceleración suficiente sobre el cerebro, pueden producirse lesiones por deformación del cráneo junto con las propias lesiones difusas ocasionadas con la aceleración del impacto.…”

“…Sin embargo, la gran variabilidad en el tipo de daños cerebrales que causa, debida al limitado control de las fuerzas biomecánicas, ha favorecido el reciente desarrollo de modelos con restricción del movimiento y con menor variabilidad inter-animal. Como las fuerzas rotacionales necesitan un incremento de energía exponencial con respecto al tamaño del cerebro para producir el mismo daño, estos modelos se han desarrollado fundamente en monos 39 , cerdos pequeños 95 , ovejas 6 y conejos 47 . Por ello actualmente son modelos experimentales poco útiles debido al alto coste y las técnicas sofisticadas que requieren los animales de gran tamaño.…”

Animal Models of Human Cerebellar Ataxias: a Cornerstone for the Therapies of the Twenty-First Century

“…A decreased expression of nitric oxide metabolites has been reported a few minutes after injury, suggesting a relationship to decreased blood flow after TBI [201]. Rotational acceleration injury mimics a rotational force against the brain and is characterized by diffuse subarachnoid hemorrhage, cortical hemorrhages, and astrogliosis [202]. Brain edema and an excitotoxic cascade result in extensive delayed neuronal cell death by apoptotic necrosis in several regions including the cerebellum [203].…”