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Advances in neuroregenerative strategies are largely hindered by the complexityof the injury or disease pathology. For example, traumatic injury to the central ner-
vous system, be it spinal cord or brain, stimulates a complex injury sequelae, com-
monly categorized into two major categories: the primary injury, known as the acute
phase, and a more complex secondary injury (Fig. 7.1 ). Immediately following
mechanical insult, the injury site swells with an infl ux of peripheral blood cells,
various cytokines, and tissue debris that contribute to a hostile, neurotoxic environ-
ment [ 9 ]. Further, the swelling of soft tissue within a confi ned space (i.e. skull or
vertebrae) leads to ischemia and cell death resulting in apoptosis of neurons and
oligodendrocytes [ 9 – 11 ]. Together, these deleterious effects culminate in the pro-
gressive loss of neural function [ 9 – 12 ]. In the coming days to weeks, the infl amma-
tory environment will continue to be stimulated and play an active role in shaping
the secondary injury environment through loss of local vasculature and degenera-
tion of surrounding myelinated axons and interneurons [ 9 , 13 ]. Finally, via the inter-
actions of a number of cytokines, growth factors, and astrocytes , a fl uid-fi lled cyst
lined with reactive astrocytes called the glial scar is left in place of the lesion. The
scar acts as a barrier between the damaged area and healthy neural tissue, and the
scar itself may extend beyond the lesion cavity boundary and acts as an impenetra-
ble barrier for the growth of new axons [ 13 , 14 ]. Many neuroscience and bioengi-
neering research efforts have focused on developing methods to circumvent these
barriers (i.e. exploring delivery options and modulating cellular environment). The
purpose of this review is to discuss key approaches in neuroregeneration along with
their benefi ts, limitations, and considerations for future research.
Fig. 7.1 General neuroinfl ammation cascade after CNS injury
A. Roussas et al.