Eurogenic regions and currently limits the ability of endogenous NSPCs to replace specific neuronal or glial types in different regions in the CNS.To further complicate matters, the injured adult CNS is an entirely different environment to the normal adult neurogenic niche or the developing nervous system, with substantial influence on NSPC function that in some instances appear to override the normal program of NSPC fate.This is particularly the case for SVZ NSPCs, which, as detailed further below, can be induced away from their normal migratory route to the OB toward the site of neural damage, a process largely induced by inflammatory mediators.After successful migration to the correct location, new neuroblasts must differentiate into the proper phenotype of neuron and integrate into local circuitry.The local circuitry to be repaired will depend on the type of damage, be it ischemic, traumatically injured PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/21516355,16644668,12075913,10933485,10826665,9622623,9004058,8310852,8162841,7951646,7615481,7457166,7454885,7443883,7443876,7394066,7370485,7352540,7342107,7332893,7229502,7207162,7125003,6996456,6979539,6882991,6794696,6791606,6584937,6441351,6424837,6423703,6411158,6405633,6405416,6224396,6211131,6145536,6123407,5570417,5561070,5457452,5452362,5129948,5087319,4937542,4920254,4918342,4784023,4751821,4667797,4614279,4501484,4479401,4456838,4453243,4414636,4390092,4214299,4150620,4150261,4127340,4111593,3978347,3929867,3797469,3683634,3653845,3381938,3338980,3227963,3151125,3080214,2955683,2891600,2512331,2136391,1640004,1626561,1268797,1260604,1221796,1197454,1140906,1128415,1128395,1128334,1108674,1099171,1090967,989396,960878,917159,906885,868618,865708,848339,793305,789083,683116,665801,638462,636711,622433,593476,499965,477589,474825,391754,372839,181193,100711,38189,32149,7795 or neurodegenerative, with some common factors and others specific to the site and type of damage.Effects of exogenous factors have been variably examined in each of theabove types of neural damage and are described below for the relevant factors.The majority of research on ectopic migration and neural differentiation of SVZderived NSPCs following neural damage has been performed by use of ischemia models and has demonstrated that cells do indeed reach the injured parenchyma (Arvidsson et al Parent et al Jin et al SundholmPeters et al Ohab et al Yamashita et al Cayre et al Young et al).It appears that the cells in general no longer migrate in a chain formation and carry on individually, with some reports describing an increase in progenitor numbers without an effect on numbers of cells in the RMS (Zhang et al b), while others report that the response to injury is at the expense of the RMS population (Jin et al Goings et al).This change in migration is the direct result of chemoattractive cues expressed from the injury site.As detailed further below, chemokines and their receptors can attract neuroblasts from the RMS.For example, Stromal cellderived factorCXCL and its receptor CXCR are upregulated at the injury site (Imitola et al Robin et al) and expression of several other chemokines and their receptors are upregulated on adult NSPCs by inflammatory cytokines, such as IFN and TNF (Turbic et al).In general ischemia models have demonstrated production of new neurons from the SVZ in damaged cortex or striatum, while injury of the cortex usually promotes the generation of astrocytes and microgliamacrophages at the site of injury, with few or no new neurons produced (Ramaswamy et al Richardson et al Kreuzberg et al Blizzard et al Zhang et al).Neurodegenerative disease models, such as Parkinson’s disease (PD) models, have also demonstrated migration of SVZ NPCs to the site of damage, with production of neurons in some cases but not others (Cooper and Isacson, Kadota et al Jing et al).The production of astrocytes and oligodendrocytes near the injury site may be a result of expression of repressors of neuronal fate (Kernie et al Shear et al Buffo et al).Further, as detailed below, administration of a variety of factors promotes neurogenesis andor gliogenesis in these beta-lactamase-IN-1 web normally nonneurogenic sites.The SVZderived NSPC response and the new cells they produce is quite variable, depending on injury type, region of neural damage, species and likely a range of other factors that remain to be defined.There is littleno evidence that SGZ hippocampal N.
