Contribution of the Runx1 transcription factor to axonal pathfinding and muscle innervation by hypoglossal motoneurons

The runt-related transcription factor Runx1 contributes to cell type specification and axonal targeting projections of the nociceptive dorsal root ganglion neurons. Runx1 is also expressed in the central nervous system, but little is known of its functions in brain development. At mouse embryonic day (E) 17.5, Runx1-positive neurons were detected in the ventrocaudal subdivision of the hypoglossal nucleus. Runx1-positive neurons lacked calcitonin gene-related peptide (CGRP) expression, whereas Runx1-negative neurons expressed CGRP. Expression of CGRP was not changed in Runx1-deficient mice at E17.5, suggesting that Runx1 alone does not suppress CGRP expression. Hypoglossal axon projections to the intrinsic vertical (V) and transverse (T) tongue muscles were sparser in Runx1-deficient mice at E17.5 compared to age-matched wild-type littermates. Concomitantly, vesicular acetylcholine transporter-positive axon terminals and acetylcholine receptor clusters were less dense in the V and T tongue muscles of Runx1-deficient mice. These abnormalities in axonal projection were not caused by a reduction in the total number hypoglossal neurons, failed synaptogenesis, or tongue muscles deficits. Our results implicate Runx1 in the targeting of ventrocaudal hypoglossal axons to specific tongue muscles. However, Runx1 deficiency did not alter neuronal survival or the expression of multiple motoneuron markers as in other neuronal populations. Thus, Runx1 appears to have distinct developmental functions in different brain regions

Glycosylation-mediated targeting of carriers

For safe and effective therapy, drugs should be delivered selectively to their target tissues or cells at an optimal rate. Drug delivery system technology maximizes the therapeutic efficacy and minimizes unfavorable drug actions by controlling their distribution profiles. Ligand-receptor binding is a typical example of specific recognition mechanisms in the body; therefore, ligand-modified drug carriers have been developed for active targeting based on receptor-mediated endocytosis. Among the various ligands reported thus far, sugar recognition is a promising approach for active targeting because of their high affinity and expression. Glycosylation has been applied for both macromolecular and liposomal carriers for cell-selective drug targeting. Recently, the combination of ultrasound exposure and glycosylated bubble liposomes has been developed. In this review, recent advances of glycosylation-mediated targeted drug delivery systems are discussed

Ossification of the ligamentum flavum

Ossification of the ligamentum flavum (OLF or OYL: ossification of the yellow ligament) usually occurs at the lower thoracic level and causes various types of neurological symptoms in accordance with the compression level of the spinal cord, the nerve roots, the conus medullaris, and the cauda equina. Although the greatest compression level to the nerve tissues is thought to be the most pathognomonic one, it is difficult to diagnose it in some cases. The effectiveness of conservative treatment such as applying a corset is small. Early surgical treatment is strongly recommended for the patients with spastic gait, severe decrease of muscle power in the lower extremities, bladder-bowel disturbance, combined ossification of the posterior longitudinal ligament at the same level, and severe compression to the spinal cord due to thickly hypertrophied ossification. However, numbness of the lower extremities and spastic gait tend to remain even after surgery

Recent Surgical Methods of Double-door Laminoplasty of the Cervical Spine (Kurokawa's Method)

Introduction: Double-door laminoplasty (DDL) of the cervical spine (Kurokawa's method) was developed as one of posterior decompression surgical methods in the late 1970s and after then has been modified by adding various procedures such as the posterior muscle handling and the use of artificial spacers. There are three principles of DDL: First, to decompress the cervical spinal cord by central splitting of the spinous processes and laminae, preserving those lengths as much as possible and widening the spinal canal space symmetrically. Second, to maintain the widened spinal canal space steadily by fixing spacers made of hydroxyapatite the contour is almost the same as the widened space. Third, to re-suture the semispinalis muscles to the C2 spinous process to restore the strength of the posterior cervical muscles. Technical note: The important technical points in performing osteotomy are as follows: At each vertebra, osteotomy is performed from the caudal side and gradually proceeds to the cranial side because there is a space between the lamina and the dura mater at the caudal side and the osteotomy can be safely made. The surgeon must pay attention to the changes in color of the osteotomy site from red of cancellous bone, to white of the inner cortex, and finally to yellow of the yellow ligament and extradural fat tissue. Attention must be paid to the changes in sound and tactile sensation delivered from the air-drill when completing osteotomy of the inner cortex of lamina. By moving an air-drill slowly, tactile sensation can be more sensitive. During osteotomy, the process must be checked frequently by touching the inner cortex of the lamina with a probe. Conclusion: At present, DDL is a useful surgical method for cervical myelopathy at multiple level lesions

Postoperative C5 Palsy: Conjectured Causes and Effective Countermeasures

Postoperative C5 palsy (C5 palsy) is defined as de novo or aggravating muscle weakness mainly at the C5 region with slight or no sensory disturbance after cervical spine surgery. The features of C5 palsy are as follows: 1) one-half of patients are accompanied by sensory disturbance or intolerable pain at the C5 region; 2) 92% of patients have hemilateral palsy; 3) almost all palsy occurs within a week after surgery; 4) the incidence is almost the same between the anterior and posterior approaches to the cervical spine; 5) the prognosis is relatively good even in patients with severe muscle weakness. Even now, the precise causes of C5 palsy have not yet been revealed. From the viewpoint of the kinds of nerve tissue involved, the uncertain causes of C5 palsy are divided into two theories: 1) the segmental spinal cord disorder theory and 2) the nerve root injury theory. In the former, the segmental spinal cord, particularly the anterior horn cells, is thought to be chemically damaged because of preoperative ischemia and/or the aggression of reactive oxygen during postoperative reperfusion. By contrast, in the latter, the anterior rootlet and/or nerve root are believed to be mechanically damaged because of compression force and/or distraction force. In this theory, the features of C5 palsy can be well explained from anatomical viewpoints. Additionally, various countermeasures have been proposed, such as the intermittent relaxation of the tension of the hooks to the multifidus muscles during surgery; prophylactic foraminotomy to decompress C5 nerve root; prevention of excessive posterior shift of the spinal cord, which may cause the tethering effect of the nerve root; and prevention of excessive postoperative lordotic alignment of the cervical spine. These countermeasures have been proved effective, and may support the nerve root injury theory as the main conjectured theory on the causes of C5 palsy

Surgical Treatment for Ossification of the Posterior Longitudinal Ligament (OPLL) at the Thoracic Spine: Usefulness of the Posterior Approach

Various methods via anterior or posterior approach with or without spinal stabilization have been performed in accordance with the level and configuration of ossification of the posterior longitudinal ligament (OPLL) as the decompression surgery for thoracic myelopathy due to OPLL. Among them, anterior decompression at the middle thoracic level (T4/T5-T7/T8) is especially difficult to perform because of the special anatomical structures, where the spinal alignment is kyphotic and the thoracic cage containing circulatory-respiratory organs exist nearby. Of the anterior decompression procedures at this level, the posterior approach has various advantages compared to the anterior one. In the anterior approach, the procedure is complicated and the effect of decompression of the spinal cord can be obtained only by direct resection or anterior floating of the OPLL. However, complications such as spinal cord injury and dural tear are most likely to occur at that time. On the contrary, in the posterior approach, the procedure is simple, and various options to obtain decompression can be selected from, these are, laminectomy, laminoplasty, dekyphosis surgery, staged decompression surgery (Tsuzuki's method), circumferential decompression via posterior approach alone (Ohtsuka's method), and circumferential decompression via combined posterior and anterior approaches (Tomita's method). Among them, in laminectomy, laminoplasty, and dekyphosis surgery, anterior decompression can be obtained to some extent without performing direct procedure on the OPLL. In Ohtsuka's method, complete decompression can be obtained via posterior approach alone, although it is somewhat technically demanding. It is preferable to drop the shaved down and separated OPLL anteriorly instead of trying to remove it completely to avoid complications, especially in patients with severe adhesion between the dura mater and OPLL