Creative Biolabs has established and validated various models of traumatic brain injury (TBI), among which the most commonly used are the weight drop, the fluid percussion, and the cortical contusion injury models. These models are useful for the assessment of new treatments designed to limit cerebral damage and/or enhance neurological recovery following TBI. Creative Biolabs conducts contract research using these models and our traumatic brain injury work covers not only short-term recovery and treatments but also longer-term functional and cognitive outcomes.
Introduction of Traumatic Brain Injury
Traumatic Brain Injury (TBI), a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. TBI is seen in a variety of forms, from local and mild injury to diffuse and severe. Mild brain injuries may cause subtle alterations of consciousness almost unnoticeable to the patient, while severe injuries have the capacity to be incompatible with life. Clinical presentations vary from an acute nature immediately after the impact to a more insidious onset due to cumulative effects over time. The pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far.
Overview of TBI Models
To understand the pathological features of TBI and evaluate potential therapeutic strategies for TBI, various animal models have been created and characterized. Each of the animal models is aimed to mimic a certain type of clinical TBI. Creative Biolabs has expertise in the following models of TBI in rats and mice:
Fluid Percussion Injury (FPI) Model
FPI is a highly characterized and widely accepted model that has been successfully applied in several animal species including rabbit, cat, rat, mouse, and pig. The injury is produced by applying a fluid pulse (~20 msec) directly onto the surface of the dura via a craniotomy, leading to brief brain tissue displacement and deformation. The injury can be applied centrally (midline FPI), over the sagittal suture midway between bregma and lambda, or laterally (lateral FPI), over the parietal cortex. This model is capable of producing graded neurological, histological, and cognitive outcomes that are similar to those seen in human TBI. By altering the severity of injury and location of the injury site, the FPI model can reproduce neurological impairments and neuropathology associated with both diffuse and focal injury.
Controlled Cortical Impact Injury (CCI) Model
The CCI model was developed in the late 1980s and rapidly became one of the most commonly used models of pre-clinical TBI. CCI is most commonly produced using a device that rapidly accelerates a rod to impact the surgically exposed cortical dural surface. A key feature of CCI is that the injury parameters (e.g., depth, velocity, and dwell time) can all be controlled for producing a broad range of TBI severities and closed head impact by impacting the intact skull. The deficits caused by CCI models have been found to mimic neurobehavioral and cognitive deficits, as they are typically seen after human TBI, such as depression, anxiety, impairment of spatial learning and memory, and multiple motor deficits.
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 caused by motor vehicle accidents or falls. This model involves head impact followed by prolonged loading into a foam pad under the animal. Depending on the severity of the injury, the induced brain injury results in hemorrhages, neuronal cell death, astrogliosis, diffuse axonal injury, and cytotoxic brain edema.
The comprehensive list of rodent neurological disease models is placed below for your review. Please click the links for more detailed description of each model:
Creative Biolabs has equipped with state-of-the-art facilities and staffed with experienced PhD-level scientists, which enables us to help to choose a most suitable model, to tailor study-specific protocols and study plans, and to obtain reliable, high-quality data. Whether the objective is to bring a compound to out-licensing stages, expand the therapeutic potential of already approved therapies or progress a compound to clinical trial phases, Creative Biolabs can help.
Contact us to find out on how we can help you move your drug or device along the development pathway.
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