Jefferson Chen

Evidence that synaptically-released zinc contributes to neuronal injury after traumatic brain injury

Prior evidence indicates that synaptically-released zinc enters postsynaptic neurons in toxic excess during ischemia and seizures. In addition, prevention of this zinc translocation has been shown to be neuroprotective in both ischemia and seizures. Here we show evidence that the same translocation of zinc from presynaptic boutons into postsynaptic neurons occurs after mechanical injury to the brain. Specifically, using a rat model of traumatic brain injury, we show that trauma is associated with (i) loss of zinc from presynaptic boutons (ii) appearance of zinc in injured neurons, and (iii) neuroprotection by intraventricular administration of a zinc chelator just prior to brain impact. The possible use of zinc chelators for neuroprotection after head trauma is considered.

Feasibility study using surface-enhanced Raman spectroscopy for the quantitative detection of excitatory amino acids

The release of excitatory amino acids (EAAs) from injured neurons has been associated with secondary injury following head trauma. The development of a rapid and sensitive method for the quantification of EAAs may provide a means for clinical management of patients affected by head trauma. We explore the potential application of surface-enhanced Raman spectroscopy (SERS) for rapid quantification of the concentration of EAAs in aqueous silver colloids. The EAAs glutamate (Glu) and aspartate (Asp) are released following head injury and have been observed to exhibit SERS spectra that should enable them to be distinguished in a complex aqueous media. Of the two EAAs, the concentration of Glu has been shown to be more indicative of injury to the central nervous system. Using 30-s scans and a 50-mW argon laser, aqueous Glu is quantifiable from 0.4 to 5 micromol/L and is spectrally distinguishable from Asp. In addition, initial in vivo microdialysis experiments suggest that this SERS system is capable of measuring chemical changes following head trauma in the rat brain. Compared with current high-performance liquid chromatography (HPLC) techniques for amino acid detection, the short scanning and processing time associated with the SERS approach enables measurement on a near-real-time basis, providing clinical information in anticipation of pharmaceutical intervention.

Detection of Pathological Zinc Accumulation In Neurons: Methods for Autopsy, Biopsy, and Cultured Tissue:

It has been repeatedly shown that synaptically released zinc contributes to excitotoxic neuronal injury in ischemia, epilepsy, and mechanical head trauma. Such zinc-induced injury leaves an unmistakable “footprint” in the injured neurons, allowing an easy and unambiguous postmortem diagnosis. This footprint is the presence of weakly bound, histochemically reactive zinc in the cytoplasm of the perikaryon and proximal dendrites. Such staining appears to be a necessary and sufficient marker for zinc-induced neuronal injury. Here we show how to prepare and stain tissue from biopsy, autopsy, or experimental animal sources for maximal contrast and visibility of zinc-injured neurons.

Pituitary tumors: surgical and medical management.

The pituitary gland has been termed the master gland because of the myriad of hormones that emanate from it that are vital for normal homeostasis as well as growth and development. Primary tumors of this region are frequent and account for up to 10% of intracranial tumors. Pituitary tumors are monoclonal in origin, and may arise from any of the different cell types of the pituitary gland. Hence, these tumors may be manifest by their hormonal secretions. This may lead to profound and striking physiological changes attributable, for example, to prolactin, growth hormone, or ACTH excess. The central location of the pituitary gland also leads to characteristic compressive symptoms. This review will explore the clinical presentations of growth hormone, ACTH, and prolactin secreting tumors as well as the non-secreting pituitary tumors. Advances in neuroimaging and neuropharmacology have resulted in changes in our treatment of these tumors. Treatment modalities including surgical, medical, and radiation therapy will be addressed. The treatment of choice is dictated by the type of tumor and the nature of the excessive hormonal expression. Outcomes and efficacy of treatment are discussed.

The value of intraoperative ultrasonography in cervical corpectomy: Assessment by postoperative computed tomography

OBJECTIVEnWe assessed the value of intraoperative ultrasonography (IUS) in cervical corpectomy by using postoperative computed tomography (CT) for comparison.nnnMETHODSnTwenty patients underwent a one-, two-, or three-level cervical corpectomy. The decompression was performed in a stepwise fashion, guided in each case by IUS findings until considered adequate. Each patient underwent postoperative CT to evaluate the accuracy of the IUS in guiding the decompression.nnnRESULTSnIn the 20 patients who underwent corpectomy, IUS guided a complete lateral gutter decompression. No evidence of asymmetry and excessive bone removal was identified by IUS at the end of the procedure. IUS was not useful in assessing the adequacy of longitudinal decompression because of the absence of neural landmarks in the sagittal plane. Postoperative CT confirmed adequate decompression in all patients. The width of decompression at the posterior margin of the vertebral body ranged from 18 to 20 mm, with a mean of 19.2 mm.nnnCONCLUSIONnWe conclude that IUS is helpful and reliable in performing a properly centered, thorough, lateral decompression in cervical corpectomy. A limited corpectomy can be started under visual guidance and then enlarged after IUS findings until complete decompression of the neural elements has been achieved. This approach avoids the problems of asymmetry, inadequate decompression, and excessive bony removal that could lead to endangerment of the vertebral artery and possible failure of the reconstruction. The accuracy of the IUS was confirmed in this study by postoperative CT.

Surface-enhanced Raman spectroscopy for the near real-time diagnosis of brain trauma in rats

The detection of sever brain trauma remains difficult when employing traditional methods in part due to the pathophysiological complexity of the condition. Current brain trauma detection includes schemes that require bulky, expensive equipment to deduce regional cerebral blood flow. These methods are difficult to use in conjunction with patients requiring ongoing intensive care and constant monitoring. Our previous studies have shown that surface- enhanced Raman spectroscopy (SERS) with silver colloids has the ability to measure physiological concentrations of in vivo brain analytes linked to brain trauma using short scan times. More recently, after implementing a damage model for ischemia in rats, an ex vivo analysis of brain microdialysis samples shows a correlation between SERS spectral features and the occurrence and location of known localized ischaemia. A near real-time measurement system could provide relevant clinical information in anticipation of surgical or pharmaceutical interventions for severely head injured patients.

Evaluation of an iPhone Otoscope in a Neurotrauma Clinic and as an Adjunct to Neurosurgical Education

Introduction CellScope®, an iPhone-enabled otoscope, was introduced into the neurotrauma clinic at an American College of Surgeons certified Level I trauma center. CellScope is an innovative tool that digitally improves optical clarity of the tympanic membrane, providing the acquisition of HIPPA compliant images. We compared the CellScope to the traditional otoscope in teaching medical students, neurosurgery physician assistants, and neurosurgery residents. In addition, the utility of this device in a neurotrauma clinic was specifically examined because of the high frequency of otologic symptoms after head trauma. Method CellScope examination of the tympanic membranes was introduced as a standard/routine part of the exam of neurotrauma patients. We retrospectively reviewed the clinic charts of the NeuroTrauma patients during a three-month time period to determine if their otologic symptoms correlated with any CellScope visualized abnormalities. Medical students, P.A.s, residents, and attendings were surveyed before and after using CellScope to assess their comfort and skill in completing an otological exam, as well as their opinion on the utility of CellScope in their medical training. Results 18 medical professionals were surveyed before and after the use of CellScope. Surveys were graded on a 1-5 scale and indicated a greater preference for the CellScope (4.7/5.0) versus the otoscope (3.16/5.0). Similarly, there was a preference for the CellScope for medical education (4.7/5.0 versus 2.78/5.0). Finally, surveys showed a greater preference for CellScope in identifying abnormal pathology. The overall score showed a 49% increased preference for CellScope over the traditional otoscope. Six previously undiagnosed abnormalities of the tympanic membrane were identified in a total of 27 neurotrauma patients using CellScope. Conclusion The visualization of the tympanic membrane is an important part of the physical examination of the neurotrauma patient. Smartphone-enabled medical instruments like CellScope may facilitate and remove barriers to routine implementation of this part of the physical examination.

Surface-enhanced Raman spectroscopy for the in-vitro and ex-vivo detection of excitatory amino acids

Traditionally methods for the detection of excitatory amino acids, which have been linked to secondary injury following head trauma, can be excessively time consuming clinically. A near real-time measurement system could provide clinical information in anticipation of pharmaceutical intervention for head injured patients. Our studies have shown that surface-enhanced Raman spectroscopy (SERS) with silver colloids has the ability to measure physiological concentrations of in vitro excitatory amino acids using short scan times. Employing a damage model for ischemia, preliminary ex vivo rat extracellular grain fluid analysis shows an intriguing correlation between SERS spectral features and expected Glutamate concentration fluctuations following head injuries.

Interactive iBook-Based Patient Education in a NeuroTrauma Clinic

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Educational interventions may alleviate the burden of TBI for patients and their families. Interactive modalities that involve engagement with the educational material may enhance patient knowledge acquisition when compared to static text‐based educational material. OBJECTIVE: To determine the effects of educational interventions in the outpatient setting on self‐reported patient knowledge, with a focus on iPad‐based (Apple, Cupertino, California) interactive modules. METHODS: Patients and family members presenting to a NeuroTrauma clinic at a tertiary care academic medical center completed a presurvey assessing baseline knowledge of TBI or concussion, depending on the diagnosis. Subjects then received either an interactive iBook (Apple) on TBI or concussion, or an informative pamphlet with identical information in text format. Subjects then completed a postsurvey prior to seeing the neurosurgeon. RESULTS: All subjects (n = 152) significantly improved on self‐reported knowledge measures following administration of either an iBook (Apple) or pamphlet (P < .01, 95% confidence interval [CI]). Subjects receiving the iBook (n = 122) performed significantly better on the postsurvey (P < .01, 95% CI), despite equivalent presurvey scores, when compared to those receiving pamphlets (n = 30). Lastly, patients preferred the iBook to pamphlets (P < .01, 95% CI). CONCLUSION: Educational interventions in the outpatient NeuroTrauma setting led to significant improvement in self‐reported measures of patient and family knowledge. This improved understanding may increase compliance with the neurosurgeons recommendations and may help reduce the potential anxiety and complications that arise following a TBI.

Interfacing with the nervous system: a review of current bioelectric technologies

The aim of this study is to discuss the state of the art with regard to established or promising bioelectric therapies meant to alter or control neurologic function. We present recent reports on bioelectric technologies that interface with the nervous system at three potential sites—(1) the end organ, (2) the peripheral nervous system, and (3) the central nervous system—while exploring practical and clinical considerations. A literature search was executed on PubMed, IEEE, and Web of Science databases. A review of the current literature was conducted to examine functional and histomorphological effects of neuroprosthetic interfaces with a focus on end-organ, peripheral, and central nervous system interfaces. Innovations in bioelectric technologies are providing increasing selectivity in stimulating distinct nerve fiber populations in order to activate discrete muscles. Significant advances in electrode array design focus on increasing selectivity, stability, and functionality of implantable neuroprosthetics. The application of neuroprosthetics to paretic nerves or even directly stimulating or recording from the central nervous system holds great potential in advancing the field of nerve and tissue bioelectric engineering and contributing to clinical care. Although current physiotherapeutic and surgical treatments seek to restore function, structure, or comfort, they bear significant limitations in enabling cosmetic or functional recovery. Instead, the introduction of bioelectric technology may play a role in the restoration of function in patients with neurologic deficits.