Ann Logan

CNS injuries : cellular responses and pharmacological strategies

Cellular Responses to Penetrating CNS Injury, M. Berry, A. Butt, and A. Logan Cellular Responses to Ischaemic CNS Injury, W.L. Maxwell Immune Response and CNS Injury, N.A. Gregson Haematogenous Cell Responses to CNS Injury, K.A. Brown and B.A. Khoshkbijari Role of Macrophages and Microglia in the Injured CNS, W.J. Streit Cellular Trafficking, A.J. Vora and K.A. Brown Microglia-Mediated Prevention of Traumatic Neurodegeneration S. Thanos, R. Naskar, and P. Heiduschka Transforming Growth Factor-b and CNS Scarring, A. Logan and M. Berry Neurotrophic Factors, T. Hagg Fibroblast Growth Factors, C. Grothe, C. Meisinger, and K. Wewetzer Index Audience Researchers and practitioners involved in: pharmacology, pathology, toxicology, neurophysiology, neuroanatomy, molecular biology, and cellular biology Medical students

Pigment Epithelium-Derived Factor Is Retinal Ganglion Cell Neuroprotective and Axogenic After Optic Nerve Crush Injury

PURPOSE To investigate neuroprotective and axogenic properties of pigment epithelium-derived factor (PEDF) in retinal ganglion cells (RGC) in vitro and in vivo. METHODS Adult rat retinal cultures were treated with combinations of PBS and PEDF with or without a cell permeable analogue of cAMP, and RGC survival and neurite lengths quantified. The optic nerves of anesthetised rats were also crushed intraorbitally to transect all RGC axons followed by intravitreal injections of either PBS, PEDF, or cAMP+PEDF every 7 days. RGC were back filled with FluoroGold to quantify RGC survival and longitudinal optic nerve sections were stained with GAP43 antibodies to detect regenerating RGC axons. RESULTS An optimal dose of 2.5 × 10(-5) μg/μL, promoted 65% more RGC survival than controls in vitro, increasing by 4.4- and 5-fold the number of RGC with neurites and the mean neurite length, respectively. Addition of cAMP with or without PEDF did not potentiate RGC survival or the mean number of RGC with neurites, but enhanced RGC neurite length by 1.4-fold, compared with PEDF alone. After optic nerve crush (ONC), PEDF protected RGC from apoptosis and increased the numbers of regenerating RGC axons in the optic nerve by 4.6- and 3.4-fold, respectively when compared with controls. cAMP did not enhance PEDF-induced RGC neuroprotection, but potentiated its neuroregenerative effects by 2- to 3-fold, increasing the number of RGC axons regenerating at 500 and 1000 μm from the lesions site. CONCLUSIONS This study is the first to demonstrate that PEDF enhances both RGC survival and axon regeneration in vitro and in vivo.

Adult Stem Cell Treatment for Central Nervous System Injury

Stem cells possess both self-renewing and multi-lineage differentiation properties and are being explored ex- tensively for use as a cellular therapy for regenerative medicine. Historically, replacement of lost neurons and restoration of neural circuits was primarily considered as the main mechanism by which stem cells restore function in the injured cen- tral nervous system (CNS). However, evidence is accumulating that implicates stem cell-derived trophic factors in the neuroprotection of compromised endogenous neurons and regeneration of their axons and dendrites. In this concise re- view, we summarise the potential of bone marrow-derived stem cells (BMSC), adipose-derived mesenchymal stem cells (AMSC), dental pulp stem cells (DPSC) and neural stem cells (NSC) to repair the injured CNS, with particular reference to spinal cord injury and optic nerve/retinal injury. # Contributed equally and were joint senior authors