Erol Tasdemiroglu

Chronic Trigeminal Ganglionectomy or Topical Capsaicin Application to Pial Vessels Attenuates Postocclusive Cortical Hyperemia but Does Not Influence Postischemic Hypoperfusion

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p < 0.01). CBF returned to preischemic levels ∼45 min after reperfusion and was reduced to ∼65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p < 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p < 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 μl) to the middle or posterior temporal branch of the MCA 10–14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (Paco2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to reduce severe cortical hyperemia.

Postischemic Cerebral Blood Flow and Neuroeffector Mechanisms

The influence of neuroeffector mechanisms in the regulation of postischemic cerebral blood flow was investigated by microsphere determination in 8 cats after chronic unilateral vascular deafferentation by trigeminal ganglionectomy. The animals were subjected to 90 min of reperfusion following 10 min of global ischemia induced by 4-vessel occlusion and systemic hypotension. Cortical hyperemia 30 min after reperfusion was attenuated by up to 48% in cortical gray matter ipsilateral to the side of trigeminal ganglionectomy (p less than 0.01). Axon reflex mechanisms involving the release of neuropeptides from peripheral sensory nerve fibers, such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin A (NKA), mediate this response. SP and NKA cause vasodilation by endothelium-dependent mechanisms (endothelium-dependent relaxing factor), whereas CGRP relaxes vascular smooth muscle by direct receptor interactions. Studies were therefore undertaken to determine the extent to which endothelium-dependent mechanisms mediate the hyperemia following global cerebral ischemia. In 7 intact cats, the postischemic response of pial arterioles to the topical application of acetylcholine (ACh; 10(-7) M), an endothelial-dependent vasodilator, was measured using a closed cranial window technique. Although ACh increased pial arteriolar caliber by 17% under resting conditions, the same dose elicited a vasoconstrictor response (87% of pre-ACh diameter 30 min after reperfusion) for the first 60 min of reperfusion after 10 min of ischemia. ACh-induced vasodilation was restored by 75 min (105%), but was less than control even at 120 min (109 vs. 117%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor-to-tumor metastasis of the central nervous system.

Tumor-to-tumor metastasis is a well recognized phenomenon. Although any tumor may be potential recipient of metastasis, renal cell carcinoma and meningioma are the most common malignant and benign recipients, respectively, whereas the lung and breast are the most common metastatic donors respectively, in both settings. Patients with hereditary cancer syndromes may be at higher risk for the development of tumor-to-tumor metastases. The most common pattern of tumor-to-tumor metastasis for intracranial neoplasms is the type in which an aggressive high-grade malignancy serves as the source of tumor and a more indolent neoplasm serves as the recipient tumor. The development of tumor metastasis from a second primary malignancy is uncommon and remains biologically puzzling. Its low incidence has made its full biological characterization evasive. Although rare, neurosurgeons should be aware of the entity of tumor-to-tumor metastasis.

Neurologic Complications of Cancer: Part 1

Neurologic complications related to cancer and its therapy are increasing due to increasing survival and therapeutic modalities in patients with cancer. Dealing with such complications requires familiarity with them and knowledge of pathophysiological events underlying cancer. In this article we aim to mention the neurological metastatic complications during the progress of cancer and its therapy.

The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats

Objective In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. Methods Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. Results In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Bax (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. Conclusion We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats.

Spondylodiscitis as a spinal complication of transrectal ultrasound-guided needle biopsy of the prostate.

Study Design. A case report. Objective. To describe the presentation of pyogenic spondylodiscitis as an iatrogenic spinal complication of a transrectal ultrasound-guided needle biopsy of the prostate (TUGNBP), despite prophylactic use of antibiotics, and discuss possible route of infection. Summary of Background Data. Pyogenic spondylodiscitis is a rare complication of TUGNBP. Several similar case reports, have been previously published, including 1 by the authors of this case report; however, in the present case, spondylodiscitis occurred despite prophylactic antibiotic use. Methods. A 59-year-old man was admitted to the neurosurgery department, experiencing severe back and bilateral leg pain for 6 weeks. His neurological examination was normal. His medical and surgical histories were unremarkable, except for a TUGNBP performed 2 months ago because of the high serum levels of prostate-specific antigen levels. At the time of the biopsy, he had been given prophylactic oral antibiotic (ciprofloxacin, 500 mg twice a day) for 2 weeks. The day after biopsy, the patient experienced intermittent high fever and fatigue, and a week after biopsy, he complained of progressive back pain. Results. After 2 weeks, whole-body bone scan with Tc99m-MDP revealed hyperactivity at the level of L4 and L5 vertebral bodies. His contrast-enhanced magnetic resonance image of the lumbar spine showed diffuse contrast enhancement vertebral bodies and intervertebral disc of L4 and L5 along with contrast-enhanced circumferential epidural mass extending from S2 to L3 levels. L4 hemilaminectomy and epidural and intradiscal abscess drainage at the L4–L5 levels were performed. The diagnosis was consistent with acute discitis with Gram (−) bacilli, and microbiological culture was positive for Escherichia coli. He received intravenous and oral antibiotics for 6 weeks. Conclusion. Acute pyogenic spondylodiscitis should be considered among the major complications of TUGNBP and may occur despite prophylactic antibiotic use.

Animal Models of Autism Spectrum Disorder

Animal models are developed to test hypotheses about causes of disease, and potential treatments. With genetic, molecular, imaging and electrophysiological studies being supported by animal models, autism research has been flourishing in recent years. On different aspects of autism research, a significant number of reviews have been published. Several of them treated animal models to help current knowledge around its etiology while some others had standpoint of species or neuroanatomical findings. In this article, we present an overview of the animal models.

Neurologic Complications of Cancer Part 2: Vascular, Infectious, Paraneoplastic, Neuromuscular, and Treatment-Related Complications

Neurologic complications related to cancer and its therapy are increasing because of increasing survival and therapeutic modalities in patients with cancer. To deal with such complications requires familiarity with them and knowledge of pathophysiologic events underlying cancer. The vascular, infectious, paraneoplastic, neuromuscular, and treatment-related neurologic complications of cancer are discussed in this article.

Inappropriate (Ectopic) Hypothalamic and Pituitary Hormone–Secreting Syndromes

Ectopic hormone production and secretion by tumors is usually an incidental finding; however, in some cases, the resultant endocrine syndrome may cause even greater morbidity, misdiagnosis, and shortening of life expectancy than the neoplasm itself. This is particularly true when a small and sometimes relatively benign tumor results in acromegaly, Cushing syndrome, and/or hyperprolactinemia. Many examples of inappropriate (ectopic) hormone production such as multiple endocrine neoplasia and McCune-Albright syndrome have been described. In this article, because of their importance for neurosurgeons, only the ectopic hypothalamic and pituitary hormone–secreting syndromes are reviewed.

SEARCHING EVIDENCES OF STROKE IN ANIMAL MODELS: A REVIEW OF DISCREPANCIES.

So far, animal models have helped us better understand the pathophysiology of the ischemic brain damage but they could not contribute so much to clinical practice. The discrepancies in results regarding neuroprotective agents in animal experiments compared to clinical trials have not been solved. Various animal models of ischemic stroke have proven efficacy of many neuroprotective agents without any considerable result in phase III clinical trials. As is well known, stroke-related focal cerebral ischemia or cardiac arrest related global cerebral ischemia are major causes of disability and death among human subjects. Animal models are essential to evaluate the therapeutic approaches for humans. In this review, we will try to answer two important questions: 1) Which factors endanger the reliability of experimental studies of stroke on animal models? 2) How can we design our experiments to reflect the neurorestoration and/or neuroprotection mechanisms following ischemic injury, when it comes to human disease?