Marmarou Weight Drop Injury Model

The impact acceleration model of diffuse traumatic brain injury (DTBI), commonly referred to as the “Marmarou” weight drop model is widely utilized to replicate DTBI, without focal lesion to characterize changes that closely parallel abnormalities characteristic of human DTBI cause by motor vehicle accidents or falls. In this chapter, we describe in detail procedures used to replicate DTBI of varying degrees of severity; the clinically relevant condition of posttraumatic hypoxia and hypotension; and experimental paradigms utilized for intraoperative multiparameter, physiological monitoring. We provide brief summaries of reproducible outcome evaluations characteristic of this model inclusive of (1) intraoperative physiological responses including mean arterial blood pressure (MABP), pH, pO2, and pCO2, and intra-cranial pressure (ICP); (2) gross and neurohistopathological outcomes; (3) functional studies that highlight somatomotor and cognitive behavioral changes; (4) in vitro outcome evaluations employing magnetic resonance imaging (MRI), 1H Magnetic resonance spectroscopy (1H MRS); and (5) high-performance liquid chromatography (HPLC) for the analysis of changes in cellular function, brain edema and cerebral metabolites including N-acetyl-aspartate (NAA) and adenosine tri-phosphate. Finally, we describe the complications associated with the use of this model, mainly technical in nature, easily overcome with repetitious practice and State limitations of this model, notably the use of multiparameter intraoperative monitoring techniques that can be costprohibi-tive due to the expense of the required equipment. We conclude by stating the major advantage of this model; it has been used extensively in the laboratory to evaluate the effect of pharmacological intervention to treat DTBI. Importantly, these treatments have recently reached Phase II & III clinical trial status.