title: G-CSF prevents caspase 3 activation in Schwann cells after sciatic nerve transection, but does not improve nerve regeneration.
abstract: Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model - nerve transection and repair - in healthy and diabetic rats. In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair. There was no difference in axonal outgrowth between G-CSF-treated and non-treated rats, regardless if healthy Wistar or diabetic Goto-Kakizaki (GK) rats were examined. However, G-CSF treatment caused a significant 13% decrease of cleaved caspase 3-positive Schwann cells at the lesion site in healthy rats, but only a trend in diabetic rats. In the distal nerve segments of healthy rats a similar trend was observed. In long-term experiments of healthy rats, regeneration outcome was evaluated at 90days after repair by presence of neurofilaments, wet weight of gastrocnemius muscle, and perception of touch (von Frey monofilament testing weekly). The presence of neurofilaments distal to the suture line was similar in G-CSF-treated and non-treated rats. The weight ratio of ipsi-over contralateral gastrocnemius muscles, and perception of touch at any time point, were likewise not affected by G-CSF treatment. In addition, the inflammatory response in short- and long-term experiments was studied by analyzing ED1 stainable macrophages in healthy rats, but in neither case was any attenuation seen at the injury site or distal to it. G-CSF can prevent caspase 3 activation in Schwann cells in the short-term, but does not detectably affect the inflammatory response, nor improve early or late axonal outgrowth or functional recovery.
authors: Department of Translational Medicine - Hand Surgery, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden. Electronic address: Hanna.Frost@med.lu.se.
authors: Hanna K
authors: HK
authors: Frost
authors: Department of Translational Medicine - Hand Surgery, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden. Electronic address: akira5152001@yahoo.co.jp.
authors: Akira
authors: A
authors: Kodama
authors: Division of Ophthalmology, Department of Clinical Sciences Lund, Lund University, SE-221 84 Lund, Sweden. Electronic address: Per.Ekstrom@med.lu.se.
authors: Per
authors: P
authors: Ekström
authors: Department of Translational Medicine - Hand Surgery, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden. Electronic address: Lars.Dahlin@med.lu.se.
authors: Lars B
authors: LB
authors: Dahlin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012583:Schwann Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D017211:Treatment Failure
chemical_list: D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: diabetes; factor G-CSF; nerve repair; peripheral nerve regeneration; rat; sciatic nerve injury