Mehmet Dumlu Aydin

Toward Changing of the Pathophysiologic Basis of Acute Hydrocephalus After Subarachnoid Hemorrhage: A Preliminary Experimental Study

BACKGROUNDnAcute hydrocephalus (ventricular enlargement within 72 hours) is a common complication in patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrospinal fluid (CSF) secretion may be increased in the early phases of SAH, but it has not been proved definitively. We studied the histologic features of choroid plexus (CP) in the early and late phases of SAH.nnnMETHODSnThis study was conducted on 20 rabbits, with 5 rabbits in the control group, 5 rabbits in the sham group, and 10 rabbits in the SAH group. In the SAH group, five of the animals were decapitated after 2 days of cisternal blood injections, and the other five animals were decapitated after 14 days of injections. The CP of lateral ventricles were obtained from coronary sections of brains at the level of the temporal horns of the lateral ventricles. Sections were stained with hematoxylin and eosin and Masson trichrome for SAH-related damage and examined stereologically to discern water-filled vesicles, which were counted. Sections were compared statistically.nnnRESULTSnThe mean numbers of water vesicles were different after SAH between the early decapitated group (group III) and the late decapitated group (group IV). The mean numbers of water vesicles were 2.80 (± 0.05) in the control group (group I), 2.76 (± 0.02) in the sham group (group II), 14.68 (± 0.06) in the early decapitated group (group III), and 4.78 (± 0.13) in the late decapitated group (group IV). Total number of fluid-filled vesicles of CP was also assessed stereologically; the total numbers were 840 (± 16) in group I, 828 (± 7) in group II, 4404 (± 19) in group III, and 1434 (± 41) in group IV. The numbers of water-filled cisterns were significantly increased in the early phases of SAH (P < 0.05).nnnCONCLUSIONSnIn SAH with aneurysm rupture, increased CSF secretion seems to be triggered by hemorrhage in the early phase, but it is not possible in the late phase because of CP degeneration. In the early phase of hemorrhage, CSF secretion may be stimulated by the irritant receptor glossopharyngeal and vagal nerve endings, which innervate the healthy CP epithelium and arteries. Our findings may be accepted as being causative. It is likewise possible that CSF blockage per se leads to hydrocephalus, and the morphologic changes are sequelae that occur later in the course of disease. This is the first study to show the water vesicles of CP as a causative factor in the development of acute hydrocephalus after SAH.

The role of ischemic neurodegeneration of the nodose ganglia on cardiac arrest after subarachnoid hemorrhage: an experimental study.

BACKGROUNDnThe heart is innervated by several systems that contribute to the control of the hearts rhythm. The cardiac fibers of the vagus nerve have an important role in the regulation of heart rhythm under many emotional and physical conditions. Severe electrocardiographic disturbances have been reported following subarachnoid hemorrhage (SAH), but ischemic neuronal degeneration of the nodose ganglion of the vagus nerve has not been previously investigated. We examined if there is a relationship between ischemic injury of the nodose ganglion of the vagus nerve and the severity of heart rhythm disorders after subarachnoid hemorrhage.nnnMETHODSnThis study was conducted on 20 rabbits. Four rabbits were used as a baseline group. Experimental subarachnoid hemorrhage was applied to half of the remaining animals (n = 8) by injecting homologous blood into the cisterna magna, and the others (SHAM group, n = 8) were injected with isotonic saline solution in the same manner. For 20 days after the injection, heart rhythm changes were observed daily. After the experiment, normal and ischemic neuron densities in the nodose ganglia of the vagus nerves were examined stereologically. The number of heart rhythm irregularities and the number of degenerated neurons in the nodose ganglia were compared statistically.nnnRESULTSnThe normal heart rhythm rate was 280 ± 45/min. At the beginning of the SAH, the average heart rate was 220 ± 30/min; about 10 hours later, it decreased to 189 ± 30/min, indicating severe bradycardia. However, after 7 days, the average heart rate had increased to 350 ± 30/min. Six animals died due to irregularities in cardiac function and respiration. Histopathological examinations showed that the average density of normal neurons in the nodose ganglion was 10,500 ± 2500 in the baseline animals and the SHAM group, but the normal neuron density was 8250 ± 1500 in survivors and 6450 ± 1330 in dead animals. The ischemic neuronal degeneration in the nodose ganglia was more severe in the dead animals than in the survivors (p < 0.0001).nnnCONCLUSIONnAfferent vagus nerves originating from the nodose ganglia have an important role in regulating heart rhythm via their afferent fibers and efferent connections. If neurons of the nodose ganglia are lesioned due to ischemic insult during subarachnoid hemorrhage, heart rhythm regulation by vagus afferent reflexes is disturbed. Vagus pathway paralysis may result in indirect sympathetic overactivity. The development of tachycardia causes depletion of the hearts reserves, and cardiac arrest may be inevitable following extensive subarachnoid hemorrhage.

Analysis of 107 civilian craniocerebral gunshot wounds

Abstract.In this study, we present a retrospective analysis of 107 cases due to civilian craniocerebral gunshot wounds that were treated by the medical faculty of Dicle University during a period of 7 years (January 1993 to January 2000). Twenty patients died at the hospital, and the deaths were determined to result from direct effects of brain damage. Coma was the best prognostic guideline. Diffuse brain damage and ventricular injury, particularly infections, were associated with poor outcome.

Leptin modulates noradrenaline release in the paraventricular nucleus and plasma oxytocin levels in female rats: a microdialysis study.

The neural control and mutual interrelationships among individual factors involved in the regulation of food intake and simultaneously related to reproduction are far from being understood. We have suggested that at least some of the effects of orexigenic and anorexigenic peptides might be mediated via noradrenaline release in the paraventricular nucleus (PVN). The main hypothesis was that leptin has an inhibitory action on oxytocin secretion and hypothalamic release of noradrenaline. Non-pregnant female rats in their diestrus were subjected to cannulation of the carotid artery and a microdialysis procedure with the probes in the hypothalamic PVN. Intra-arterial administration of cholecystokinin-8 (CCK) at the dose of 50 mg/kg was used to induce oxytocin and noradrenaline release. Leptin (10 mg/5 ml) was intracerebroventricularly injected in addition to CCK. Blood and microdialysis samples were collected at 20-min intervals for 80 min. Central administration of leptin significantly reduced both plasma oxytocin and hypothalamic noradrenaline responses to CCK at 20 min following the treatments. In conclusion, leptin may inhibit oxytocin secretion by lowering noradrenergic neurotransmission in the PVN. The modulator effect of leptin on noradrenaline release in the PVN may be related to feeding behavior.

Effects of pinealectomy and exogenous melatonin on ghrelin and peptide YY in gastrointestinal system and neuropeptide Y in hypothalamic arcuate nucleus: immunohistochemical studies in male rats.

It is reported that the pineal gland and its main hormone melatonin may have a role in the regulation of ghrelin synthesis in the brain. Stomach is the place where ghrelin is predominantly expressed and secreted. One aim of this study was to investigate possible effects of pinealectomy and melatonin treatment on gastric ghrelin amount. The studies on the effects of the pineal gland on leptin and ghrelin arises the question whether the pineal gland has also effects on the other energy-regulatory peptides such as peptide YY (PYY) and neuropeptide Y (NPY). Therefore, we also aimed to investigate the changes in the immunohistochemical staining of intestinal PYY and hypothalamic NPY following pinealectomy and melatonin treatment. Serum PYY levels were also investigated. Sprague-Dawley rats were divided into four groups as sham-operated (SHAM), sham-operated with melatonin treatment (SHAM-MT), pinealectomised (PNX) and melatonin-treated PNX (PNX-MT) groups. The cells immunostained for ghrelin were abundant throughout the gastric mucosa in all the groups. Neither pinealectomy nor exogenous melatonin affected significantly immunohistochemical staining of ghrelin in stomach. Pinealectomy resulted in a significant increase in immunohistochemical staining of PYY in ileum. The results of serum PYY measurement corresponded closely to the data obtained by immunohistochemical analysis of PYY in ileum, being significantly lower and higher in SHAM and PNX groups, respectively. Pinealectomy caused a decrease in NPY synthesis in ARC as understood from low immunohistochemical staining of NPY. Melatonin treatment increased NPY synthesis in SHAM rats and restored reduction in NPY synthesis caused by pinealectomy. In conclusion, the pineal gland and its main hormone melatonin can be suggested to have a role in the regulation of NPY synthesis in ARC and PYY in gastrointestinal system.

Role of degenerated neuron density of dorsal root ganglion on anterior spinal artery vasospasm in subarachnoid hemorrhage: experimental study.

BackgroundThe spinal arteries are innervated by several systems that contribute to the control of spinal cord blood flow. The sensory fibers of upper cervical nerves have vasodilatatory effect on the anterior spinal arteries (ASA). Subarachnoid hemorrhage (SAH) causes severe vasospasm by various neurochemical mechanisms. We examined whether there is a relationship between the neuron density of the C3 dorsal root ganglion and the severity of ASA vasospasm in SAH.MethodsThis study was conducted on 20 rabbits. Four of them were used as baseline group. Experimental SAH has been applied to all of 16 animals by injecting homologous blood into cisterna magna. After 20xa0days of injection, ASA and C3 dorsal root ganglia (C3DRG) were examined histopathologically. ASA volume values and normal and degenerated neuron densities of C3DRG were estimated stereologically and the results were analyzed statistically.ResultsThe mean ASA volume was 1,010u2009±u2009450xa0mm3, and the mean neuronal density of C3DRG was 10,500u2009±u2009850 in all animals. The mean volume value of ASA was 970u2009±u2009150xa0mm3, and the normal neuron density of C3DRG fell to 8,600u2009±u2009400/mm3 in slight vasospasm group. In severe vasospasm-developed animals, mean volume value of ASA was 540u2009±u200990xa0mm3 and the normal neuron density of C3DRG fell to 5,500u2009±u2009360/mm3. An inverse relationship between the degenerated neuronal density of the C3DRG and ASA volume values may indicate the severity of ASA vasospasm.ConclusionThe neuron density of C3DRG may be an important factor on the regulation of ASA volume values and the continuation of spinal cord blood flow. Low neuron density of C3DRG may be considered as an important factor in the pathogenesis of severe ASA vasospasm in SAH.

Effects of pinealectomy and exogenous melatonin on immunohistochemical ghrelin staining of arcuate nucleus and serum ghrelin leves in the rat

Although the main source of circulating ghrelin is the stomach, it is also present in physiologically relevant amounts in the hypothalamus. It is reported that pharmacological doses of melatonin decrease blood levels of ghrelin. Thus, melatonin (MT) may be a candidate for the regulation of ghrelin synthesis in the brain. This study was therefore undertaken to investigate possible effects of pinealectomy and exogenous melatonin on hypothalamic ghrelin amount. Serum ghrelin levels following pinealectomy and administration of melatonin were also sought. Adult male Sprague-Dawley rats were divided into four groups as sham-operated (SHAM), sham-operated with melatonin treatment (SHAM-MT), pinealectomised (PNX) and melatonin-treated PNX (PNX-MT) groups. Ghrelin staining in the hypothalamus was determined by immunohistochemistry. Hypothalamic ghrelin was not observed in PNX rats. Much higher staining was detected in SHAM-MT rats compared to SHAM group. Lack of effect of melatonin on hypothalamic ghrelin in PNX rats implicates that exogenous melatonin requires an intact pineal to exert its effects. Although there were remarkable changes in the immunohistochemical activity of ghrelin in the hypothalamic arcuate nucleus, neither pinealectomy nor exogenous melatonin significantly changed serum levels of ghrelin. We have demonstrated for the first time that the pineal gland may play a role in ghrelin amount in the hypothalamus.

First report of important causal relationship between the Adamkiewicz artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: An experimental study using a rabbit model

Background: The blood supply of the lower spinal cord is heavily dependent on the artery of Adamkiewicz. The goal of this study was to elucidate the effects of lumbar subarachnoid hemorrhage (SAH) on the lumbar 4 dorsal root ganglion (L4DRG) cells secondary to Adamkiewicz artery (AKA) vasospasm. Materials and Methods: This study was conducted on 20 rabbits, which were randomly divided into three groups: Spinal SAH (n = 8), serum saline (SS) (SS; n = 6) and control (n = 6) groups. Experimental spinal SAH was performed. After 20 days, volume values of AKA and neuron density of L4DRG were analyzed. Results: The mean alive neuron density of the L4DRG was 15420 ± 1240/mm3 and degenerated neuron density was 1045 ± 260/mm3 in the control group. Whereas, the density of living and degenerated neurons density were 12930 ± 1060/mm3 and 1365 ± 480/mm3 in serum saline (SS), 9845 ± 1028/mm3 and 4560 ± 1340/mm3 in the SAH group. The mean volume of imaginary AKAs was estimated as 1,250 ± 0,310 mm3 in the control group and 1,030 ± 0,240 mm3 in the SF group and 0,910 ± 0,170 mm3 in SAH group. Volume reduction of the AKAs and neuron density L4DRG were significantly different between the SAH and other two groups (P < 0.05). Conclusion: Decreased volume of the lumen of the artery of Adamkiewicz was observed in animals with SAH compared with controls. Increased degeneration the L4 dorsal root ganglion in animals with SAH was also noted. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

Uncovering a New Cause of Obstructive Hydrocephalus Following Subarachnoid Hemorrhage: Choroidal Artery Vasospasm–Related Ependymal Cell Degeneration and Aqueductal Stenosis—First Experimental Study

BACKGROUNDnHydrocephalus is a serious complication of subarachnoid hemorrhage (SAH). Obstruction of the cerebral aqueduct may cause hydrocephalus after SAH. Although various etiologic theories have been put forward, choroidal artery vasospasm-related ependymal desquamation and subependymal basal membrane rupture as mechanisms of aqueductal stenosis have not been suggested in the literature.nnnMETHODSnThis study was conducted on 26 hybrid rabbits. Five rabbits were placed in a control group, 5 were placed in a sham group, and the remaining rabbits (nxa0= 16) were placed in the SAH group. In the first 2 weeks, 5 animals in the SAH group died. The other 21 animals were decapitated after the 4-week follow-up period. Choroidal artery changes resulting from vasospasm, aqueduct volume, ependymal cell density, and Evans index values of brain ventricles were obtained and compared statistically.nnnRESULTSnMean aqueduct volume was 1.137 mm(3) ± 0.096, normal ependymal cell density was 4560/mm(2) ± 745, and Evans index was 0.32 ± 0.05 in control animals (nxa0= 5); these values were 1.247 mm(3) ± 0.112, 3568/mm(2) ± 612, and 0.34 ± 0.15 in sham animals (nxa0= 5); 1.676 mm(3) ± 0.123, 2923/mm(2) ± 591, and 0.43 ± 0.09 in animals without aqueductal stenosis (nxa0= 5); and 0.650 mm(3) ± 0.011, 1234/mm(2) ± 498, and 0.60 ± 0.18 in animals with severe aqueductal stenosis (nxa0= 6). The choroidal vasospasm index values were 1.160 ± 0.040 in the control group, 1.150 ± 0.175 in the sham group, 1.760 ± 0.125 in the nonstenotic group, and 2.262 ± 0.160 in the stenotic group. Aqueduct volumes, ependymal cell densities, Evans index, and choroidal artery vasospasm index values were statistically significantly different between groups (P < 0.05).nnnCONCLUSIONSnEpendymal cell desquamation and subependymal basal membrane destruction related to choroidal artery vasospasm may lead to aqueductal stenosis and hydrocephalus after SAH.

Unraveling of the Effect of Nodose Ganglion Degeneration on the Coronary Artery Vasospasm After Subarachnoid Hemorrhage: An Experimental Study.

BACKGROUNDnCardiac arrest is a major life-threatening complication of subarachnoid hemorrhage (SAH). Although medullary cardiocirculatuar center injury and central sympathetic overactivity have been suspected of initiating coronary artery spasm-induced cardiac arrest, we aimed to elucidate the effects of vagal ischemia at the brainstem on coronary vasospasm and sudden death in SAH.nnnMETHODSnTwenty-six rabbits were randomly divided into 3 groups. Control (n = 5); SHAM (n = 8), and SAH group (n = 13). Experimental SAH was applied by injecting homologous blood into the cisterna magna, and the SHAM group was injected with isotonic saline solution also in the cisterna magna., Twenty-one days after the injection, histopathologic changes of the neuron density of nodose ganglia, the vasospasm index values of the coronary arteries, and the electrocardiographic events were analyzed.nnnRESULTSnIncreased vasospasm index of the coronary arteries and degenerated neuron density of nodose ganglion were significantly different between animals with SAH, control, and SHAM groups (P < 0.005). If neurons of the nodose ganglia are lesioned due to ischemic insult during SAH, the heart rhythm regulation by vagus afferent reflexes is disturbed.nnnCONCLUSIONSnWe found that there is causal relationship between nodose ganglion degeneration and coronary vasospasm. Our finding could be the reason that many cardiac events occur in patients with SAH. Vagal pathway paralysis induced by indirect sympathetic overactivity may trigger coronary vasospasm and heart rhythm disturbances. Our findings will aid in the planning of future experimental studies and in determining the clinical relevance of such studies.