Karin R. Swartz

Interleukin-6 promotes post-traumatic healing in the central nervous system

The central nervous system (CNS) is an immune-privileged site where the role of immune cells and mediators in traumatic brain injury is poorly understood. Previously we have demonstrated that interleukin (IL)-6, a cytokine that acts on a wide range of tissues influencing cell growth and differentiation, is an agonist for vascular endothelial growth factor (VEGF), in in vitro vascularization assays for brain microvessel endothelial cells. In this present work we focus on the role of IL-6 in promoting tissue repair in the CNS in vivo. An aseptic cerebral injury (ACI) was created in the right parietal cortex, using both wild type (C57Bl/6J) and IL-6-deficient (C57Bl/6J-IL-6-/-) mice to study the consequences of the absence of IL-6 on the pathology of brain injuries. We monitored the immediate, early, and late responses to this traumatic injury by characterizing several histologic features in the CNS at days 1, 4, 7 and 14 following injury. Acellular necrosis, cellular infiltration, and re-vascularization were characterized in the injured tissues, and each of these histologic features was individually graded and totaled to assign a healing index. IL-6-deficient mice were found to have a comparatively slower rate of recovery and healing. Furthermore, fluorescein isothiocyanate (FITC)-dextran intravenous injection demonstrated leaky vessels in IL-6-deficient but not in wild type animals following ACI. Additionally, chronic expression of IL-6 in the CNS using transgenic GFAP-IL-6 mice resulted in more rapid healing following ACI. The accelerated tissue repair in GFAP-IL-6 transgenic animals is primarily due to extensive re-vascularization as detected by endothelial cell markers. Combined, this data suggests an important role of IL-6 in tissue repair processes following traumatic injury in the CNS.

Effects of progesterone on experimental spinal cord injury

Progesterone has been proposed to be protective to the central nervous system following injury. This study assessed progesterone supplementation in the setting of contusional spinal cord injury in male and female rats. Short-term (5 days of either 4 or 8 mg/kg progesterone) and long-term (14 days of either 8 or 16 mg/kg progesterone) therapy failed to show any significant alteration in locomotor functioning and injury morphometrics after 21 days. This study does not support progesterone as a potential therapeutic agent in spinal cord injury.

Functional MR imaging assessment of a non-responsive brain injured patient

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Vessel microport technique for applications in cerebrovascular research

Cerebrovascular research suffers from a lack of reliable methods with which to deliver exogenous substances effectively into the central nervous system (CNS) of small experimental animals. Here we describe a novel vessel microport surgical technique for a variety of cerebrovascular applications that is reproducible and well tolerated in mice. The procedure is based on the insertion of a vessel microport into the external carotid artery for substance delivery into the CNS via the internal carotid artery. The method results in selective substance delivery into the ipsilateral hemisphere. Other novel aspects of this surgical technique include the ability to perform multiple injections, study of conscious mice well removed from surgery, and lack of occlusion of the common or internal carotid artery that allows carotid flow to be maintained. The feasibility of this technique has been validated by infusion of HIV Tat protein to induce permeability of the blood–brain barrier and by implantation of tumor cells to establish a brain metastasis model. Thus, the described vessel microport technique can be employed in a variety of cerebrovascular research applications.

Kümmell's disease: a case report and literature review.

Study Design. A case report and literature review of Kümmell’s disease. Objective. To describe a case that meets modern criteria for Kümmell’s disease and discuss the literature on this. Summary of Background Data. Over 100 years ago, Hermann Kümmell described a condition in which patients sustained a “trivial” trauma, had an essentially asymptomatic period lasting weeks to months, then developed a painful, progressive angular kyphosis. Only with the advent of radiograph technology, and the radiographic demonstration of delayed vertebral body collapse, was this concept felt to be valid. There has been a renewed interest in this as a diagnostic entity. Methods. A patient is presented who developed worsening midback pain weeks after a minor fall. He subsequently was found to have T9, and T10 destructive vertebral body lesions. Results. Only after an extensive workup, including 3 biopsies of the affected area was the diagnosis of Kümmell’s disease considered and surgical treatment performed. Conclusion. Delayed vertebral body collapse, i.e., Kümmell’s disease, needs to be considered in any patient with recurrent or worsening spinal symptoms. Under-recognition of this condition leads to delayed diagnosis and treatment.

Deficiency of telomerase activity aggravates the blood–brain barrier disruption and neuroinflammatory responses in a model of experimental stroke

Epidemiology and genetic studies indicate that patients with telomere length shorter than average are at higher risk of dying from heart disease or stroke. Telomeres are located at the ends of eukaryotic chromosomes, which demonstrate progressive length reduction in most somatic cells during aging. The enzyme telomerase can compensate for telomere loss during cell replication. The present study sought to investigate the contribution of telomerase to stroke and blood–brain barrier (BBB) dysfunction. Telomerase reverse transcriptase knockout (TERT−/−) mice and littermate controls with normal TERT expression were subjected to a 24‐hr permanent middle cerebral artery occlusion (pMCAO). The stroke outcomes were assessed in terms of neurological scores and infarct volumes. In addition, we evaluated oxidative stress, permeability across the BBB, and integrity of tight junctions in brain microvessels. Neurological testing revealed that TERT−/− mice showed enhanced deficits compared with controls. These changes were associated with a greater infarct volume. The expression of tight junction protein ZO‐1 decreased markedly in ischemic hemispheres of TERT−/− mice. The brain microvessels of TERT−/− mice also were more susceptible to oxidative stress, revealing higher superoxide and lower glutathione levels compared with mice with normal TERT expression. Importantly, TERT deficiency potentiated the production of inflammatory mediators, such as tumor necrosis factor‐α, interleukin‐1β, and intercellular adhesion molecule‐1, in the ischemic hemispheres of mice with pMCAO. Our study suggests that TERT deficiency can predispose to the development of stroke in an experimental model of this disease.

Quadriparesis and spinal cord stimulation: case report.

Study Design. Case report. Objective. To report the occurrence of a rare complication following revision of a spinal cord stimulator. Summary of Background Data. Puncture of the dura with placement of an electrode within the spinal cord has not been reported as a complication of spinal cord stimulation. Methods. A patient presented with upper and lower extremity weakness following inadvertent placement of an electrode into the spinal cord. The clinical case is presented as well as review of the literature. Results. The patient had the electrode successfully removed; however, her neurologic status deteriorated. Conclusion. Revision of spinal cord stimulators is usually a safe procedure. However, placement of an electrode within the spinal cord during the revision process is a potential complication resulting in severe neurologic injury.

Unilateral calf hypertrophy seen in lumbosacral stenosis: case report and review of the literature.

Study Design. A case report of a patient with neurogenic unilateral calf hypertrophy and review of the literature are reported. Objectives. To provide further evidence that S1 radiculopathy is predisposed to develop neurogenic muscle hypertrophy. Summary of Background Data. Calf hypertrophy, specifically hypertrophy of the gastrocnemius muscle, is a rare but recognized presentation of S1 and less commonly L5 radiculopathies. The pathophysiology of this is incompletely understood. Methods. We present a 59-year-old patient with painless progressive distal right leg weakness and calf enlargement. Electrodiagnostic studies and MAGNETIC RESONANCE IMAGING scanning were performed to evaluate the extent and cause of radicular damage as the etiology for unilateral calf hypertrophy. Results. Examination and electrodiagnostic studies revealed right L5, right S1, and left L5 radiculopathies. Imaging studies demonstrated lumbar stenosis at L3–L4, L4–L5, and L5–S1 vertebral levels as well as L4–L5 and L5–S1 foraminal stenosis. After decompressive surgery the progressive nature of the patient’s symptomatology halted, and he had partial resolution of his deficits. Conclusion. Although the patient had bilateral L5 radiculopathies, he only had hypertrophy in the distribution of his right S1 radiculopathy. This supports the hypothesis that dysfunction of the S1 nerve root or its distribution is a predisposing factor to develop neurogenic muscle hypertrophy. Furthermore, patients presenting with unilateral calf hypertrophy need a careful diagnostic evaluation for S1 radiculopathy as well as to exclude asymmetric presentation of systemic neuromuscular conditions.

Craniocervical Anomalies in Dubowitz Syndrome

Dubowitz syndrome is a disorder involving craniofacial abnormalities, growth retardation and mental retardation. Approximately 142 cases have been reported, with various associated other anomalies. These include cardiovascular, urogenital and endocrine abnormalities, as well as a predisposition to infections and hematological malignancies. Scoliosis has been described in association with this syndrome, as have isolated vertebral abnormalities. There has, however, been no description of craniocervical abnormalities. We describe three Dubowitz patients with significant craniocervical abnormalities.

Noninvasive evaluation of electrical stimulation impacts on muscle hemodynamics via integrating diffuse optical spectroscopies with muscle stimulator

Abstract. Technologies currently available for the monitoring of electrical stimulation (ES) in promoting blood circulation and tissue oxygenation are limited. This study integrated a muscle stimulator with a diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively quantify muscle blood flow and oxygenation responses during ES. Ten healthy subjects were tested using the integrated system. The muscle stimulator delivered biphasic electrical current to right leg quadriceps muscle, and a custom-made DCS flow-oximeter was used for simultaneous measurements of muscle blood flow and oxygenation in both legs. To minimize motion artifact of muscle fibers during ES, a novel gating algorithm was developed for data acquisition at the time when the muscle was relaxed. ES at 2, 10, and 50 Hz were applied for 20 min on each subject in three days sequentially. Results demonstrate that the 20-min ES at all frequencies promoted muscle blood flow significantly. However, only the ES at 10 Hz resulted in significant and persistent increases in oxy-hemoglobin concentration during and post ES. This pilot study supports the application of the integrated system to quantify tissue hemodynamic improvements for the optimization of ES treatment in patients suffering from diseases caused by poor blood circulation and low tissue oxygenation (e.g., pressure ulcer).