Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from graymatter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.

The brain grows with age in non-human primates (NHPs). Therefore, atlas-based stereotactic coordinates cannot be used directly to target subcortical structures if the size of the animal's brain differs from that used in the stereotactic atlas. Furthermore, growth is non-uniform across different cortical regions, making it difficult to simply apply a single brain-expansion ratio. We determined the skull reference lines that best reflect changes in brain size along the X, Y, and Z axes and plotted the changes in reference-line length against the changes in body weight. The skull reference lines had a linear relationship with body weight. However, comparison of skull reference lines with body weight confirmed the non-uniform skull growth during postnatal development, with skull growth more prominent in the X and Y axes than the Z axis. Comparing the differences between the atlas-based lengths and those calculated empirically from plot-based linear fits, we created craniometric indices that can be used to modify stereotactic coordinates along all axes. We verified the accuracy of the corrected stereotactic targeting by infusing dye into internal capsule in euthanized and preserved NHP brains. Our axis-specific, craniometric-index-adjusted stereotactic targeting enabled us to correct for targeting errors arising from differences in brain size. Histological verification showed that the method was accurate to within 1 mm. Craniometric index-adjusted targeting is a simple and relatively accurate method that can be used for NHP stereotactic surgery in the general laboratory, without the need for high-resolution imaging.
Body Weight ; Brain ; Internal Capsule ; Methods ; Primates ; Skull

BACKGROUND: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. METHODS: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. RESULTS: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. CONCLUSIONS: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.
Astrocytes ; Axons ; Coloring Agents ; Extremities ; Glial Fibrillary Acidic Protein ; Gliosis ; Gray Matter ; Internal Capsule* ; Ischemia ; Microscopy ; Models, Animal ; Models, Theoretical ; Myelin Sheath ; Necrosis ; Neurons ; Oligodendroglia ; Organelles ; Pathology ; Plastics ; Prevalence ; Recovery of Function ; Rupture ; Stroke ; White Matter

Spinal pain is a common symptom that motivates visiting a physician. However, the natural course is usually benign and few patients need invasive treatment. Even though history taking, neurological examination, and imaging studies provide useful information for understanding the etiology of spinal pain, the pain chart is the most important tool for decision making regarding spinal interventions. Invasive treatments for chronic spinal pain refractory to conservative management include surgery as well as established interventions such as medial branch blocks, nerve root blocks, the sacroiliac joint block, and radiofrequency neurotomy, as well as emerging procedures such as pressure-controlled discography and percutaneous epidural adhesiolysis. Surgery should be considered for patients with a progressive neurologic deficit including significant radiculopathy, failure of spinal interventions, or an uncertain or serious diagnosis.
Decision Making ; Diagnosis ; Humans ; Nerve Block ; Neurologic Examination ; Neurologic Manifestations ; Pain Management ; Radiculopathy ; Sacroiliac Joint ; Spine

OBJECTIVE: Vertebral distraction is routinely performed during anterior cervical discectomy and fusion (ACDF). Overdistraction can injure the facet joints and may cause postoperative neck pain consequently. The purpose of this study was to investigate the clinical relevance of distraction force during ACDF. METHODS: This study included 24 consecutive patients with single level cervical disc disease undergoing single level ACDF. We measure the maximum torque just before the the arm of the Caspar retractor was suspended by the rachet mechanism by turning the lever on the movable arm using a torque meter. In order to turn the lever using the torque driver, we made a linear groove on the top of the lever. We compared the neck disability index (NDI) and visual analogue scale (VAS) scores between the high torque group (distraction force>6 kgf.cm) and the low torque group (distraction force< or =6 kgf.cm) at routine postoperative intervals of 1, 3, 5 days and 1, 3, 6 months. RESULTS: The VAS scores for posterior neck pain had a linear correlation with torque at postoperative 1st and 3rd days (y=0.99x-1.1, r2=0.82; y=0.77x-0.63, r2=0.73, respectively). VAS scores for posterior neck pain were lower in the low torque group than in the high torque group on both 1 and 3 days postoperatively (3.1+/-1.3, 2.6+/-1.0 compared with 6.0+/-0.6, 4.9+/-0.8, p<0.01). However, the difference in NDI scores was not statistically significant in all postoperative periods. CONCLUSION: Vertebral distraction may cause posterior neck pain in the immediate postoperative days. We recommend not to distract the intervertebral disc space excessively with a force of more than 6.0 kgf.cm.
Arm ; Diskectomy ; Humans ; Intervertebral Disc ; Neck ; Neck Pain ; Pain, Postoperative ; Spinal Fusion ; Torque ; Zygapophyseal Joint

OBJECTIVE: The purpose of this study is to find the optimal stiffness and volume of bone cement and their biomechanical effects on the adjacent vertebrae to determine a better strategy for conducting vertebroplasty. METHODS: A three-dimensional finite-element model of a functional spinal unit was developed using computed tomography scans of a normal motion segment, comprising the T11, T12 and L1 vertebrae. Volumes of bone cement, with appropriate mechanical properties, were inserted into the trabecular core of the T12 vertebra. Parametric studies were done by varying the volume and stiffness of the bone cement. RESULTS: When the bone cement filling volume reached 30% of the volume of a vertebral body, the level of stiffness was restored to that of normal bone, and when higher bone cement exceeded 30% of the volume, the result was stiffness in excess of that of normal bone. When the bone cement volume was varied, local stress in the bony structures (cortical shell, trabecular bone and endplate) of each vertebra monotonically increased. Low-modulus bone cement has the effect of reducing strain in the augmented body, but only in cases of relatively high volumes of bone cement (>50%). Furthermore, varying the stiffness of bone cement has a negligible effect on the stress distribution of vertebral bodies. CONCLUSION: The volume of cement was considered to be the most important determinant in endplate fracture. Changing the stiffness of bone cement has a negligible effect on the stress distribution of vertebral bodies.
Bone Cements ; Finite Element Analysis ; Spine ; Sprains and Strains ; Vertebroplasty

OBJECTIVE: To evaluate the effects of electric cortical stimulation in the experimentally induced focal traumatic brain injury (TBI) rat model on motor recovery and plasticity of the injured brain. METHOD: Twenty male Sprague-Dawley rats were pre-trained on a single pellet reaching task (SPRT) and on a Rotarod task (RRT) for 14 days. Then, the TBI model was induced by a weight drop device (40 g in weight, 25 cm in height) on the dominant motor cortex, and the electrode was implanted over the perilesional cortical surface. All rats were divided into two groups as follows: Electrical stimulation (ES) group with anodal continuous stimulation (50 Hz and 194 micros duration) or Sham-operated control (SOC) group with no electrical stimulation. The rats were trained SPRT and RRT for 14 days for rehabilitation and measured Garcia's neurologic examination. Histopathological and immunostaining evaluations were performed after the experiment. RESULTS: There were no differences in the slice number in the histological analysis. Garcia's neurologic scores & SPRT were significantly increased in the ES group (p<0.05), yet, there was no difference in RRT in both groups. The ES group showed more expression of c-Fos around the brain injured area than the SOC group. CONCLUSION: Electric cortical stimulation with rehabilitation is considered to be one of the trial methods for motor recovery in TBI. However, more studies should be conducted for the TBI model in order to establish better stimulation methods.
Animals ; Brain ; Brain Injuries ; Electric Stimulation ; Electrodes ; Humans ; Male ; Motor Cortex ; Neurologic Examination ; Plastics ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: The biomechanical properties of the Coflex(TM) (Paradigm Spine, NY, USA), a device designed to provide dynamic stabilization without lumbar fusion, have not been clearly defined. The purpose of this study was to determine the efficacy and biomechanical effect of Coflex(TM) using finite element model (FEM). METHODS: A 3D geometric model of the L3-L5 was created by integrating computerized tomography (CT) images. Based on the geometric model, a 3D FEM was created and the Coflex(TM) model was incorporated into the base model. Mechanical load dependent on the postural changes and boundary conditions, were imposed to simulate various 3D physiological states. The simulation analysis included stress and strain distributions, intervertebral disc deformation, and the range of motion of the facet joint and lumbar spinous process. RESULTS: Coflex(TM) significantly restrained displacement in extension, lateral bending and compression of joint between the L4-5 as one in the experimental group was observed -1.3% of flexion, -24.5% of extension, -44.5% of lateral bending and -37.2%. The average intradiscal pressure of the L4-5 decreased by 63% and the average facet contract force of the L4-5 decreased markedly by 34% in the experimental group. A load of 120 MPa from extension was observed at the base of spinous process in the experimental group. CONCLUSION: The Coflex(TM) can be safely used for achieving functional dynamic stabilization of the lumbar vertebral column while preserving the intactness of the other components. However, the fatigue fracture of the L4 spinous process should be carefully monitored.
Contracts ; Displacement (Psychology) ; Equipment Design ; Finite Element Analysis ; Fractures, Stress ; Intervertebral Disc ; Joints ; Lumbar Vertebrae ; Range of Motion, Articular ; Spine ; Sprains and Strains ; Zygapophyseal Joint

Angiocentric glioma was recently recognized as a distinct clinicopathological entity in the 2007 World Health Organization classification of tumors of the central nervous system. Typically, it presents with seizure in children and young adults. However, our patient did not have a history of seizure. Seizure did not occur up to 6 months after operation. Although it usually does not have calcification brain magnetic resonance imaging in our patient showed T1-hyperintense and T2-hypointense signals with calcification.
Brain ; Calcinosis ; Central Nervous System ; Child ; Glioma ; Humans ; Magnetic Resonance Imaging ; Neoplasms, Neuroepithelial ; Seizures ; World Health Organization ; Young Adult

We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin+ NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin+ NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke.
Cold Temperature ; Corpus Callosum ; Emigration and Immigration ; Immunohistochemistry ; Intermediate Filament Proteins ; Light ; Magnetic Resonance Imaging ; Models, Theoretical ; Motor Cortex ; Nerve Tissue Proteins ; Neural Stem Cells ; Neurons ; Rats, Sprague-Dawley ; Rose Bengal ; Stem Cells ; Stroke ; Transplants