Specialized In Vivo Evaluations

Specialized in vivo evaluations available at Southern Research include the following:

• Blood-Brain Barrier Penetration Studies. Brain or cerebral spinal fluid (CSF) levels of the administered test article are measured to assess diffusion into the CNS space. These studies have been conducted using various routes of administration, including IV and intracerebral dosing, in various preclinical small animal models. Data from these studies have been used to determine biodistribution and brain/plasma or CSF/plasma drug level ratios for small molecules and biologics, including viral vectors, neural peptides, chemotherapeutic agents, antipsychotics, narcotic analgesics, and various compounds for substance abuse.
• Neurotoxicity. Body movements are controlled by a complex series of ascending, descending, and integratory nervous system components coupled with a normal musculoskeletal system. Causes of gait disturbances are varied and consist of degeneration of specific aspects of the nervous system. Gait disturbances may be described as loss of sensation, movement, or position (proprioceptive deficits); abnormalities in movement due to loss of visual acuity; failure of the sense of gravity or motion (vestibular ataxia); and failure of proper motor coordination (cerebellar ataxia). The objective of neurotoxicity evaluations is to determine the effects of a candidate drug on the central nervous system and/or the peripheral nervous system in adult and developing animals.

The following neurobehavioral assessments and neuropathology services are available:

• Functional Observational Battery. The functional observational battery (FOB) is a noninvasive neurobehavioral assessment designed to systematically evaluate the effect of a drug on a rodent's neurobehavior; this procedure is used to detect gross functional deficits. FOB assessments may be performed as stand-alone studies (typically for assessment of acute effects) or may be included as evaluations within general toxicity studies (typically for assessment of subchronic or cumulative effects). The data from the FOB for a given test article are used to identify potential neurotoxic effects that may require follow up using specialized toxicity tests. Generally, the series of tests in the FOB proceeds from the least interactive to the most interactive measurements.
• Rotarod. The degree of animal activity measured by an automatic apparatus is another useful neurobehavioral assessment. One such measurement is a performance test based on forced motor activity on a rotating rod, usually by a rodent, termed Rotarod. At a fixed time after dosing, an animal is placed on a rotating rod, and the time between animal placement on the Rotarod and the time the animal falls off is measured (seconds). All animals are trained to the apparatus prior to the day of dosing. The test is used to evaluate balance and coordination of the subject, particularly in experimental animal models for neurological disorders, and to assess drug effects.
• Neuropathology. In addition to neurobehavioral assessments, neurotoxicity assessments may include specialized histopathological analyses of nervous system tissues prepared by in situ perfusion with an aldehyde fixative. For general purposes, the hematoxylin-eosin (H&E) stain demonstrates the basic structures and cytoarchitectures of tissues; however, for neurohistopathology, perfusion fixation and special staining are more effective.

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