Authors:
Ning Zhang
Summary:
Following TBI, injury and inflammation of brain tissue result in the swelling of various structures within a finite and constricting space. In addition to the mechanical injury to the cells, the elevated pressure due to brain tissue swelling leads to the release of compounds that cause secondary injury to healthy brain tissue beyond the primary insult. Persistent cell dysfunction and poor neural regenerative capabilities at the TBI site and beyond lead to the formation of a lesion defect or cavity that is associated with prolonged neurological impairment. Conventional treatments for TBI have been focused on managing the primary injury using hypothermia, osmotic therapy, and decompressive craniectomy, as well as neuroprotection with pharmacological agents to reduce the secondary damage. Despite the benefit in small numbers of patients, none of these treatments have been translated into clear improvements in the mortality and neurological outcome. This is perhaps due to the inability of these treatments to repopulate the lesion with functional neural cells. In alignment with this notion, neural transplantation strategies have been tested to reconstruct the lesion cavity. Despite its efficacy in providing sustained functional recovery in some CNS diseases, neural transplantation for TBI repair has had limited success, due to poor donor cell survival and functionality at the lesion site. In particular, the ongoing tissue inflammation and scarring at the lesion site and the lack of any supportive tissue structure and vasculatures within the cavity present a hostile environment that jeopardizes the survival of transplanted cells. For cell replacement at the TBI lesion cavity, there is a critical need to pre-condition the lesion site with vasculature network to support subsequently arriving neural cells/precursors. To this end, we have developed an in-situ cross-linking hydrogel with similar mechanical property to that of native brain tissue and cell adhesive motifs. We have demonstrated for the first time the formation of a well-structured vasculature network within the injected hydrogel at the TBI lesion cavity without the use of angiogenic growth factors. Further, to improve functional recovery, we transplanted human neural stem cells with neural differentiation factors to the TBI lesion using our hydrogel as carrier, and significant functional recovery was found after 8 weeks of treatment.
Source:
Military Health Research Forum 2009; Hallmark Crown Center, Kansas City, Missouri (08/31/09-09/03/09)