%0 Journal Article
%T Hippocampal Neurogenesis and the Brain Repair Response to Brief Stereotaxic Insertion of a Microneedle
%A Shijie Song
%A Shuojing Song
%A Chuanhai Cao
%A Xiaoyang Lin
%A Kunyu Li
%A Vasyl Sava
%A Juan Sanchez-Ramos
%J Stem Cells International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/205878
%X We tested the hypothesis that transient microinjury to the brain elicits cellular and humoral responses that stimulate hippocampal neurogenesis. Brief stereotaxic insertion and removal of a microneedle into the right hippocampus resulted in (a) significantly increased expression of granulocyte-colony stimulating factor (G-CSF), the chemokine MIP-1a, and the proinflammatory cytokine IL12p40; (b) pronounced activation of microglia and astrocytes; and (c) increase in hippocampal neurogenesis. This study describes immediate and early humoral and cellular mechanisms of the brain¡¯s response to microinjury that will be useful for the investigation of potential neuroprotective and deleterious effects of deep brain stimulation in various neuropsychiatric disorders. 1. Background Deep brain stimulation through chronically implanted metal electrodes into specific brain regions is becoming a common therapeutic choice for medication refractory movement disorders such as Parkinson¡¯s disease (PD), tremors, and dystonia (see reviews [1¨C3]). More recently, DBS has been applied to psychiatric and behavioral disorders including depression, obsessive compulsive disorder, and addiction and most recently to disorders of consciousness [4¨C9]. Long-term implantation of a fine metal electrode, even without chronic electrical stimulation may produce unwanted effects. Neuropathological examination of brain tissue from patients with DBS revealed activated astrocytes and microglia regardless of the underlying disease [10¨C15]. Electrical stimulation is not required to see signs of neuroinflammation; inflammatory changes have been observed around recording electrodes used for characterizing epileptogenic tissue and around CSF fluid shunt catheters [16, 17]. To understand the earliest reactions to implantation of a metal electrode, we studied the cellular and cytokine responses over time to transient insertion of a fine needle (maximum diameter of 200£¿¦̀m) into the dorsal hippocampus of the mouse. We tested the hypothesis that the creation of a focal microlesion in hippocampus elicits self-repair mechanisms mediated by cytokines which activate microglia, promote astrocytosis, and stimulate stem/progenitor cells to proliferate and generate new neurons. 2. Materials and Methods All procedures described here were reviewed and approved by the IACUC Committee of the University of South Florida and the Haley VA Research Service. 2.1. Animals C57BL/6 mice, 8¨C10 weeks old, were purchased from Harlan Laboratories, and transgenic GFP mice (C57BL/6-Tg [ACTB-EGFP] 1Osb/J, 003291) were purchased
%U http://www.hindawi.com/journals/sci/2013/205878/