Nervous system injury and regeneration

Dr. Munira ShahbuddinArtificial Tissue Engineering

Nervous System Injuryand Regeneration

• The nervous system in vertebrates is composed of

two main divisions: the peripheral nervous system(PNS) and the central nervous system (CNS). TheCNS includes the brain and the spinal cord; the

PNScontains the cranial, spinal, and autonomic nerves,which (along with their branches) connect to theCNS

Neurodegenerative disease

• Damage to the nervous system can occur due to ischemic, chemical, mechanical, or thermal factors.

• In addition to triggering a variety of cellular and molecular events, these insults may lead to transection

of nerves, interruption of communications between nerve cell bodies and their supporting cells, disruption of the interrelations between neurons and their supporting cells, and the disruption of the blood nerve barrier.

• In the CNS, axons do not regenerate in their native environment in response to injury. Myelin debris and other types of glycoproteins at the injury site are inhibitory for axonal regeneration. The presence of the blood-brain barrier retards the migration of macrophages to the injury site for debris clearance.

• Glial cells, such as astrocytes, do not provide trophic support for axonal regeneration.

• The ability of nerves to regenerate is highly dependent on the location of the damage, whether it is on the nerve tract that connects PNS to PNS, CNS to CNS, or PNS to CNS.

Tissue Engineering Strategiesfor Nervous System Repair

• Use of nerve guidance channels is a promising nerve graft alternative.

• A variety of channels presenting physical, chemical, mechanical, and biological guidance cues to regenerating nerves have been developed with the potential for nerve repair following PNS and spinal cord injuries, and neurodegenerative pathologies [e.g., Parkinson’s disease (PD)]

TE strategies

• Tissue engineering strategies for nervous system repair can be separated into four categories.

• These include axonal guidance devices, cell population recovery, drug delivery, and electrical stimulation.

Repairing damaged brain• The scientists genetically modified retroviruses to carry genes for the

transcription factor Sox2, which is known to play an important role in the development of stem cells. The team injected the viruses into the damaged brains of mice, where they incorporated the genetic information into cells.

• This transformed adult NG2 glia cells (which normally help maintain the physical structure of the brain and supply it with nutrients) into neurons. The new neurons only grew in the injured areas and did not grow in the brains of uninjured mice.

• By measuring the electrical conductance of the new cells, the scientists were able to confirm that the new neurons had been incorporated into the brain’s neural networks and could receive signals.

• Tissue engineering approaches hold great promise for neural tissue repair/regeneration. Advances in developmental biology, biomaterials, cell and molecular biology, and neuroscience have furthered our understanding of the neural tissue formation process and environmental cues necessary for neural tissue regeneration.

• Mimicry of these biological, chemical and mechanical cues by creating cell-scaffold constructs based on tissue engineering principles would direct and accelerate the tissue regeneration process, leading to enhanced anatomical reconstruction and functional restoration.