A comprehensive analysis integrating phenotypic assessment uncovering thornless cultivar lineages in Aralia elata.

Aralia elata is an Araliaceae woody plant species found in Northeastern Asia. To understand how genetic pools are distributed for A.elata clones, we were to analyze the population structure of A.elata cultivars and identify how these are correlated with thorn-related phenotype which determines the utility of A.elata. We found that the de novo assembled genome of 'Yeongchun' shared major genomic compartments with the public A.elata genome assembled from the wild-type from China. To identify the population structure of the 32 Korean and Japanese cultivars, we identified 44 SSR markers and revealed three main sub-clusters using ΔK analysis with one isolated cultivar. Machine-learning based clustering with thorn-related phenotype correlated moderately with population structure based on SSR analysis suggested multi-layered genetic regulation of thorn-related phenotypes. Thus, we revealed genetic lineage of A.elata and uncovered isolated cultivar which can provide new genetic material for further breeding.

CyberKnife based fractionated stereotactic radiotherapy as an upfront treatment for cerebral arteriovenous malformation.

BACKGROUND: To explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). METHODS: Between January 2008 and October 2020, 45 patients underwent CKFRT for cerebral AVMs as a first treatment. The delineation of AVM targets included AVM nidus. The mean target volume was 4.07 cm3, and 9 lesions (20%) were larger than 10.0 cm3. The mean marginal dose was 24 Gy (range, 20-35 Gy). CKFRT was delivered in median 3 fractions (range, 2 âˆ¼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. RESULTS: During a median follow-up of 47 (5-148) months, complete obliteration and partial obliteration of AVM after CKFRT were obtained in 23 (51%) and 13 (29%) patients, respectively. Median time to complete obliteration was 39 (15-63) months. The cumulative probability of complete obliteration rate at 3 years was 47%. Complete obliteration rate of AVM was associated with Radiosurgery-based AVM score, which was consisted of AVM volume, patients age, and AVM location. One (2%) patient had hemorrhage during the follow-up period. CONCLUSIONS: CKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.

A review of the complexity adjustment in the Korean Diagnosis-Related Group (KDRG).

BACKGROUND: The Korean Diagnosis-Related Groups (KDRG) was revised in 2003, modifying the complexity adjustment mechanism of the Australian Refined Diagnosis-Related Groups (AR-DRGs). In 2014, the Complication and Comorbidity Level (CCL) of the existing AR-DRG system was found to have very little correlation with cost. OBJECTIVE: Based on the Australian experience, the CCL for KDRG version 3.4 was reviewed. METHOD: Inpatient claim data for 2011 were used in this study. About 5,731,551 episodes, which had one or no complication and comorbidity (CC) and met the inclusion criteria, were selected. The differences of average hospital charges by the CCL were analysed in each Adjacent Diagnosis-Related Group (ADRG) using analysis of variance followed by Duncan's test. The patterns of differences were presented with R 2 in three patterns: The CCL reflected the complexity well (VALID); the average charge of CCL 2, 3, 4 was greater than CCL 0 (PARTIALLY VALID); the CCL did not reflect the complexity (NOT VALID). RESULTS: A total of 114 (19.03%), 190 (31.72%) and 295 (49.25%) ADRGs were included in VALID, PARTIALLY VALID and NOT VALID, respectively. The average R 2 for hospital charge of CCL was 4.94%. The average R 2 in VALID, PARTIALLY VALID and NOT VALID was 4.54%, 5.21%, and 4.93%, respectively. CONCLUSION: The CCL, the first step of complexity adjustment using secondary diagnoses, exhibited low performance. If highly accurate coding data and cost data become available, the performance of secondary diagnosis as a variable to reflect the case complexity should be re-evaluated. IMPLICATIONS: Lack of reviewing the complexity adjustment mechanism of the KDRG since 2003 has resulted in outdated CC lists and levels that no longer reflect the current Korean healthcare system. Reliable cost data (vs. charge) and accurate coding are essential for accuracy of reimbursement.

Factors influencing the incidence and treatment of intracranial aneurysm and subarachnoid hemorrhage: time trends and socioeconomic disparities under an universal healthcare system.

BACKGROUND: Despite increasing usage of endovascular treatments for intracranial aneurysms, few research studies have been conducted on the incidence of unruptured aneurysm (UA) and subarachnoid hemorrhage (SAH), and could not show a decrease in the incidence of SAH. Moreover, research on socioeconomic disparities with respect to the diagnosis and treatment of UA and SAH is lacking. METHOD: Trends in the incidences of newly detected UA and SAH and trends in the treatment modalities used were assessed from 2005 to 2015 using the nationwide database of the Korean National Health Insurance Service in South Korea. We also evaluated the influence of demographic characteristics including socioeconomic factors on the incidence and treatment of UA and SAH. RESULT: The rates of newly detected UA and SAH were 28.3 and 13.7 per 100 000 of the general population, respectively, in 2015. The incidence of UA increased markedly over the 11-year study period, whereas that of SAH decreased slightly. UA patients were more likely to be female, older, employee-insured, and to have high incomes than SAH patients. In 2015, coiling was the most common treatment modality for both UA and SAH patients. Those who were female, employee-insured, or self-employed, with high income were likely to have a higher probability to be treated for UA and SAH. CONCLUSION: The marked increase in the detection and treatment of UA might have contributed to the decreasing incidence of SAH, though levels of contribution depend on socioeconomic status despite universal medical insurance coverage.

Outcomes of Stenting versus Endarterectomy for Symptomatic Extracranial Carotid Stenosis: A Retrospective Multicenter Study in Korea.

BACKGROUND: The present multicenter retrospective study aimed to compare the outcome of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) among Korean patients with symptomatic extracranial carotid stenosis. METHODS: Between January 2008 and December 2011, 677 patients underwent either CAS (346, 51.1%) or CEA (331, 48.9%). The primary end point included the occurrence of major adverse cardiovascular events (MACEs), defined as fatal or nonfatal stroke and myocardial infarction, and all-cause mortality during the periprocedural period and within 4 years after CAS or CEA. RESULTS: Although patients undergoing CAS and CEA did not differ significantly in MACE incidence within 4 years (15.3% vs. 11.5%, P = 0.14), CEA showed lower periprocedural MACE incidence than CAS with clinical significance (6.1% vs. 3.0%, P = 0.06). During the periprocedural period, the incidence of any stroke was significantly higher in patients undergoing CAS (5.5% vs. 2.4%, P = 0.04) but not the incidence of myocardial infarction (0.6% vs. 0.3%, P > 0.99). Kaplan-Meier survival analysis showed similar MACE-free (P = 0.16), stroke-free (P = 0.24), and overall survival (P = 0.25) rates in both groups. On subgroup analysis, patients older than 70 years undergoing CAS had a significantly higher incidence of MACE at 4 years (22.7% vs. 13.7%, P = 0.03). CONCLUSIONS: Although the risk of MACE did not differ significantly within 4 years in this Korean population undergoing CAS and CEA, there was a higher risk of stroke with CAS during the periprocedural period.

A Faster and Wider Skin Incision Technique for Decompressive Craniectomy: n-Shaped Incision for Decompressive Craniectomy.

OBJECTIVE: Decompressive craniectomy (DC) is a useful surgical method to achieve adequate decompression in hypertensive intracranial patients. This study suggested a new skin incision for DC, and analyzed its efficacy and safety. METHODS: In the retrograde reviews, 15 patients underwent a newly suggested surgical approach using n-shape skin incision technique (Group A) and 23 patients were treated with conventional question mark skin incision technique (Group B). Two groups were compared in the terms of the decompressed area of the craniectomy, protruded brain volume out of the skull layer, the operation time from skin incision to bone flap removal, and modified Rankin Scale (mRS) which was evaluated for 3 months after surgery. RESULTS: The decompressed area of craniectomy (389.1 cm2 vs. 318.7 cm2, p=0.041) and the protruded brain volume (151.8 cm3 vs. 116.2 cm3, p=0.045) were significantly larger in Group A compared to the area and the volume in Group B. The time interval between skin incision and bone flap removal was much shorter in Group A (23.3 minutes vs. 29.5 minutes, p=0.013). But, the clinical results were similar between 2 groups. Group A showed more favorable outcome proportion (mRS 0-3, 6/15 patients vs. 5/23 patients, p=0.225) and lesser mortality cases proportion 1/15 patients vs. 4/23 patients, but these differences were not significantly observed (p=0.225 and 0.339). CONCLUSION: DC using n-shaped skin incision was a feasible and safe surgical technique. It may be an easier and faster method for the purpose of training neurosurgeons.

Three-year follow-up of blood pressure after treating hypertensive patients with symptomatic carotid artery stenosis.

BACKGROUND: Blood pressure (BP) was reported to decrease significantly after carotid endarterectomy (CEA) or carotid stenting (CAS) up to the 1-year follow-up. We evaluated changes in BP for 3 years after treating hypertensive patients with symptomatic carotid artery stenosis by either CEA or CAS and determined predisposing factors for normotensive BP at the 3-year follow-up. METHODS: A total of 123 hypertensive patients with at least 3 years of clinical and radiographic follow-up after treatment were included in this study and placed in the CEA (n = 65) or CAS group (n = 58). BP changes for 3 years, the number of patients with a normotensive BP (≤120/80 mmHg), and the percentage decrease in BP were evaluated and compared between groups. RESULTS: Compared to pretreatment BP, the CEA group had significantly decreased BP at the 1- and 2-year follow-up (p < 0.05), but not the 3-year follow-up. The CAS group had significantly decreased BP at the 1-, 2-, and 3-year follow-up (p < 0.05). Stenosis location (body lesions over apical lesions; OR = 1.526, 95 % CI, 1.341 to 6.224; p = 0.034) was an independent predisposing factor for normotensive BP at the 3-year follow-up. CONCLUSIONS: For hypertensive patients with symptomatic carotid artery stenosis, BP was lowered at 3 years after both CEA and CAS compared to pretreatment BP. CAS might lower BP better over the long term than did CEA, and hypertensive patients with stenosis at body lesions might be normotensive at 3 years after CEA or CAS.

Clinical, Radiologic, and Pathologic Findings of Subdural Osteoma: A Case Report.

We present a case of a subdural osteoma. A 29-year-old female presented with a 3-year history of headaches. Computed tomography scan revealed a homogeneous high-density lesion isolated from the inner table of the frontal bone (a lucent dural line) in the right frontal convexity. Magnetic resonance imaging revealed an extra-axial lesion with a broad base without dural tail sign and punctate enhancement pattern characteristic of abundant adipose tissue. Upon surgical excision, we found a hard bony mass clearly demarcated from the dura. The mass displayed characteristics of an osteoma upon histological examination. The symptom was relieved after operation.

Early Decompression of Acute Subdural Hematoma for Postoperative Neurological Improvement: A Single Center Retrospective Review of 10 Years.

OBJECTIVE: This study was conducted to investigate survival related factors, as well as to evaluate the effects of early decompression on acute subdural hematoma (ASDH). METHODS: We retrospectively reviewed cases of decompressive craniectomy (DC) for decade. In total, 198 cases of DC involved ASDH were available for review, and 65 cases were excluded due to missing data on onset time and a delayed operation after closed observation with medical care. Finally, 133 cases of DC with ASDH were included in this study, and various factors including the time interval between trauma onset and operation were evaluated. RESULTS: In the present study, survival rate after DC in patients with ASDH was shown to be related to patient age (50 years old, p=0.012), brain compression ratio (p=0.042) and brain stem compression (p=0.020). Sex, preoperative mental status, and time interval between trauma onset and operation were not related with survival rate. Among those that survived (n=78), improvements in Glasgow Coma Scale (GCS) score of more than three points, compared to preoperative measurement, were more frequently observed among the early (less than 3 hours between trauma onset and operation) decompressed cases (p=0.013). However, improvements of more than 4 or 5 points on the GCS were not affected by early decompression. CONCLUSION: Early decompression of ASDH was not correlated with survival rate, but was related with neurological improvement (more than three points on the GCS). Accordingly, early decompression in ASDH, if indicated, may be of particular benefit.

Delayed Vertebral Artery Dissection after Posterior Cervical Fusion with Traumatic Cervical Instability: A Case Report.

Vascular injury presented immediately after the penetration, but delayed onset of vascular symptom caused by an embolism or vessel dissection after cervical fusion or traumatic event is extremely rare. We present a case of a 56-year-old woman who underwent an operation for cervical fusion for type II Odontoid process fracture. She presented symptoms of seizure with hemiparesis in 6 days after the operation. Multifocal acute infarction due to an embolism from the left VA (V3 segment) dissection was observed without a definite screw breach the transverse foramen. We hereby reported the instructive case report of delayed onset of vertebral artery dissection after posterior cervical fusion with type II odontoid process fracture patient. When a cervical operation performed in the cervical trauma patient, even if no apparent VA injury occurs before and during the operation, the surgeon must take caution not to risk cerebral infarction because of the delayed VA dissection.

A case of hemifacial spasm caused by an artery passing through the facial nerve.

Hemifacial spasm (HFS) is a clinical syndrome characterized by unilateral facial nerve dysfunction. The usual cause involves vascular compression of the seventh cranial nerve, but compression by an artery passing through the facial nerve is very unusual. A 20-year-old man presented with left facial spasm that had persisted for 4 years. Compression of the left facial nerve root exit zone by the anterior inferior cerebellar artery (AICA) was revealed on magnetic resonance angiography. During microvascular decompression surgery, penetration of the distal portion of the facial nerve root exit zone by the AICA was observed. At the penetrating site, the artery was found to have compressed the facial nerve and to be immobilized. The penetrated seventh cranial nerve was longitudinally split about 2 mm. The compressing artery was moved away from the penetrating site and the decompression was secured by inserting Teflon at the operative site. Although the facial spasm disappeared in the immediate postoperative period, the patient continued to show moderate facial weakness. At postoperative 12 months, the facial weakness had improved to a mild degree. Prior to performing microvascular decompression of HFS, surgeons should be aware of a possibility for rare complex anatomy, such as compression by an artery passing through the facial nerve, which cannot be observed by modern imaging techniques.

Cervical arthroplasty for moderate to severe disc degeneration: clinical and radiological assessments after a minimum follow-up of 18 months--Pfirrmann grade and cervical arthroplasty.

PURPOSE: Clinical outcomes and radiologic results after cervical arthroplasty have been reported in many articles, yet relatively few studies after cervical arthroplasty have been conducted in severe degenerative cervical disc disease. MATERIALS AND METHODS: Sixty patients who underwent cervical arthroplasty (Mobi-C®) between April 2006 and November 2011 with a minimum follow-up of 18 months were enrolled in this study. Patients were divided into two groups according to Pfirrmann classification on preoperative cervical MR images: group A (Pfirrmann disc grade III, n=38) and group B (Pfirrmann disc grades IV or V, n=22). Visual analogue scale (VAS) scores of neck and arm pain, modified Oswestry Disability Index (mODI) score, and radiological results including cervical range of motion (ROM) were assessed before and after surgery. RESULTS: VAS and mean mODI scores decreased after surgery from 5.1 and 57.6 to 2.7 and 31.5 in group A and from 6.1 and 59.9 to 3.7 and 38.4 in group B, respectively. In both groups, VAS and mODI scores significantly improved postoperatively (p<0.001), although no significant intergroup differences were found. Also, cervical dynamic ROM was preserved or gradually improved up to 18 months after cervical arthroplasty in both groups. Global, segmental and adjacent ROM was similar for both groups during follow-up. No cases of device subsidence or extrusion were recorded. CONCLUSION: Clinical and radiological results following cervical arthroplasty in patients with severe degenerative cervical disc disease were no different from those in patients with mild degenerative cervical disc disease after 18 months of follow-up.

Influence of Moyamoya disease on psychopathological abnormality in young males in Korea: analysis of multiphasic personal inventory test.

We analyzed the results of a multiphasic personal inventory test to confirm whether Moyamoya disease (MMD) affects the psychopathology in a group of young male Koreans. The authors manually reviewed the results of the Korean military multiphasic personal inventory (KMPI) for the examination of conscripts in Korea from July 2006 to May 2010. The normal volunteers group (N = 200) was composed of those males who do not have any brain disease or brain trauma. The MMD group (N = 37) was composed of those with MMD. There were more abnormal results in the MMD group (32.4 %) than in the normal volunteers group (13.0 %, p < 0.001). Results of the Neurosis Set showed that the anxiety scale, the depression scale and the somatization scale were more increased in the MMD group than that in the normal volunteer group (p = 0.014, 0.002 and 0.006, respectively). Results of the Social Relation Set showed that the aggregation scale was more increased in the MMD group than that in the normal volunteers group (p = 0.017). Young males with MMD may have more tendencies to have abnormal results of a multiphasic personal inventory test as compared to that of normal volunteers, suggesting that MMD may cause psychopathology in young Korean males.

Improvement in sensory function via granulocyte-macrophage colony-stimulating factor in rat spinal cord injury models.

OBJECT: The aim in this study was to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) leads to sensory improvement in rat spinal cord injury (SCI) models. METHODS: Thirty male Sprague-Dawley rats were included in this study: 10 in the sham group (laminectomy alone without SCI), 10 in the SCI group (SCI treated with phosphate-buffered saline), and 10 in the GM-CSF treatment group (SCI treated with GM-CSF). A locomotor function test and pain sensitivity test were conducted weekly for 9 weeks after SCI or sham injury. Spinal tissue samples from all rats were immunohistochemically examined for the expression of calcitonin gene-related peptide (CGRP) and abnormal sprouting at Week 9 post-SCI. RESULTS: Granulocyte-macrophage colony-stimulating factor treatment improves functional recovery after SCI. In the tactile withdrawal threshold and frequency of the hindlimb paw, the GM-CSF group always responded with a statistically significant lower threshold than the SCI group 9 weeks after SCI (p < 0.05). The response of the forelimb and hindlimb paws to cold in the GM-CSF group always reflected a statistically significant lower threshold than in the SCI group 9 weeks after injury (p < 0.05). Decreased CGRP expression, observed by density and distribution area, was noted in the GM-CSF group (optical density 113.5 ± 20.4) compared with the SCI group (optical density 143.1 ± 18.7; p < 0.05). CONCLUSIONS: Treatment with GM-CSF results in functional recovery, improving tactile and cold sense recovery in a rat SCI model. Granulocyte-macrophage colony-stimulating factor also minimizes abnormal sprouting of sensory nerves after SCI.

Effects of carotid artery stenosis treatment on blood pressure.

OBJECT: The purpose of this study was to evaluate and compare the long-term effects of carotid endarterectomy (CEA) and carotid artery stenting (CAS) on blood pressure (BP). METHODS: Between January 2003 and December 2009, 134 patients underwent 145 procedures for treatment of carotid artery stenosis. Patients with at least 1 year of clinical and radiographic follow-up after treatment were included in this study. A total of 102 patients met this criterion and were placed in the CEA group (n = 59) or the CAS group (n = 43) according to their treatment. The percentage change in BP decrement and the number of patients with a normotensive BP were evaluated and compared between the groups. RESULTS: There were no significant differences between the groups with regard to baseline characteristics. Compared with the pretreatment BP, the follow-up BPs were significantly decreased in both groups. At the 1-year followup, the percentage change in the BP decrement was greater in the CAS group (percentage change: systolic BP 9.6% and diastolic BP 12.8%) than in the CEA group (percentage change: systolic BP 5.9% [p = 0.035] and diastolic BP = 8.1% [p = 0.049]), and there were more patients with a normotensive BP in the CAS group (46.5%) than in the CEA group (22.0%, p = 0.012). CONCLUSIONS: Both CEA and CAS have BP-lowering effects. Carotid artery stenting seems to have a better effect than CEA on BP at the 1-year follow-up.

Cerebrovascular disease and stroke in Korean male adolescent.

PURPOSE: This study aimed to estimate the prevalence and incidence of cerebrovascular disease (CVD) and stroke in Korean male adolescents. MATERIALS AND METHODS: The authors reviewed all medical certificates, medical records, and radiologic images from the examinations of Korean military conscription from January 2008 to May 2011. RESULTS: Of the 101,156 examinees, 40 had CVD and stroke during adolescence. The overall prevalence and incidence of CVD and stroke was 39.54 cases per 100,000 adolescents and 2.08 cases per 100,000 adolescents per year, respectively and these were similar to the worldwide data. There were 3 cases of aneurysm, 3 cases of dural arteriovenous fistula, 11 cases of arteriovenous malformation, 4 cases of cavernous hemangioma, 4 cases of cerebrovascular infarction, 16 cases of Moyamoya disease, and 1 case of missing data. The incidence of arteriovenous malformation (0.57 cases per 100,000 adolescents per year) was lower than the incidence for the worldwide general population. The incidence of Moyamoya disease was higher than that in any other country (15.82 cases per 100,000 adolescents, vs. 0.83 cases per 100,000 adolescents per year). CONCLUSION: We observed ischemic and hemorrhagic stroke, each accounting for approximately half of cases, and high incidence of Moyamoya disease with low incidence of arteriovenous malformation in Korean male adolescents.

Endovascular treatment of basilar artery trunk aneurysms.

BACKGROUND: There has been little reported on the endovascular experience of basilar artery (BA) trunk aneurysms due to its low incidence. The purpose of this study is to report the results of endovascular treatment (EVT) of BA trunk aneurysms. METHODS: Between 2004 and 2008, eight BA trunk aneurysms were treated by EVT. Five patients presented with subarachnoid hemorrhage, one had intracranial mass effect, and in two of the patients the aneurysms were found incidentally. Four lesions were saccular aneurysms, three of them were found with BA fenestration. Three lesions were dissecting aneurysms and one was a giant fusiform aneurysm. The mean follow-up period of clinical outcome was 17.1 months (range, 6-32 months). Angiographic follow-up data was obtained in six patients for period of a mean of 15.6 months (range, 6-25 months). RESULTS: Four patients with saccular aneurysms were treated by stent-assisted coil embolization except for one patient that was treated without a stent. Three patients with dissecting aneurysms were treated by a single stent placement. One of these dissecting aneurysms rebled in 4 days after stent placement and was secured by BA occlusion. One giant fusiform aneurysm was treated by bilateral vertebral artery (VA) occlusion after balloon test occlusion. Six patients (75.0%) had excellent or good clinical outcomes, one patient whose aneurysm rebled became vegetative, and one patient with bilateral VA occlusion died. Follow-up angiograms showed that four lesions had complete occlusion and two had neck remnant. CONCLUSIONS: The endovascular catheterization of these lesions tends to be relatively simple compared to more complex neurosurgical approaches. EVT, especially using a stent, could be a valuable therapeutic method in treating BA trunk aneurysms.

Granulocyte macrophage-colony stimulating factor shows anti-apoptotic activity in neural progenitor cells via JAK/STAT5-Bcl-2 pathway.

Recently, many studies have shown that granulocyte macrophage-colony stimulating factor (GM-CSF) has anti-apoptotic activity and regulates the expression of anti-apoptotic genes including Bcl-2 family proteins in neuronal cells in vitro and in vivo. This study investigated detailed mechanism of GM-CSF involved in its anti-apoptotic activity and regulation of Bcl-2 expression in neural progenitor cells (NPCs) as a model. NPCs were cultured from the brain of E13 ICR mouse. When NPCs were treated with staurosporine at 1 µM, apoptosis occurred in more than 30% of cells in TUNEL assay. However, apoptosis was significantly inhibited by pre-treatment with GM-CSF at 10 ng/ml. Under the same experimental condition, the expression of both Bcl-2 and Bcl-xl was clearly induced by GM-CSF regardless of staurosporine treatment in RT-PCR and Western blot analyses. GM-CSF was shown to induce the expression of Bcl-2 and Bcl-xl via Janus tyrosine kinase (JAK) but not via phosphatidylinositol 3-kinase (PI3K) or RAS-mitogen activated protein kinase kinase-1 (MEK-1) using specific signal pathway inhibitors. Further analyses showed that the expression of Bcl-2 and Bcl-xl was induced by GM-CSF via signal transducers and activators of transcription 5 (STAT5) and STAT3, respectively. In addition, JAK/STAT5-Bcl-2 pathway but not JAK/STAT3-Bcl-xl pathway was responsible for the anti-apoptotic activity of GM-CSF in NPCs in TUNEL assay. To our knowledge, this study is the first report that shows differential roles of Bcl-2 and Bcl-xl, and their regulation mechanism involved in the anti-apoptotic activity of GM-CSF in NPCs.

Reduction in programmed cell death and improvement in functional outcome of transient focal cerebral ischemia after administration of granulocyte-macrophage colony-stimulating factor in rats. Laboratory investigation.

OBJECT: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against CNS injury. In this paper, the authors investigated the neuroprotective effect of GM-CSF on neuron survival and locomotor behavior in a rat model of focal cerebral ischemic injury. MATERIALS: To understand its neuroprotective effect in vitro, GM-CSF was administered to a glutamate-induced excitotoxicity neuronal injury cell culture model that mimics the pathophysiology of focal hypoxic cerebral injury. In the animal study, the authors prepared a rat focal cerebral ischemia model by occluding the unilateral middle cerebral artery. They then examined the effects of GM-CSF administration on changes in infarct volume, apoptosis-related gene expression, and improvement in locomotor behavior. RESULTS: Treatment with GM-CSF significantly increased cell viability in a cell culture model of glutamate-induced neuronal injury. Furthermore, in vivo administration of GM-CSF at 60 microg/kg body weight daily for 5 consecutive days beginning immediately after injury decreased infarction volume, altered the expression of several apoptosis-related genes (Bcl-2, Bax, caspase 3, and p53), and improved locomotor behavior in the focal cerebral ischemia model. CONCLUSIONS: The GM-CSF had neuroprotective effects in in vitro and in vivo experiments and resulted in decreased infarction volume and improved locomotor behavior. Although the specific mechanism involved in stroke recovery was not fully elucidated as it was not the primary focus of this study, administration of GM-CSF appeared to decrease the extent of neuronal apoptosis by modulating the expression of several apoptosis-related genes such as Bcl-2, Bax, caspase 3, and p53. Further investigations are necessary to better understand the role of GM-CSF on neural regeneration during the recovery phase of a stroke, as well as the intracellular signal transduction pathways that mediate neuroprotection.