Tarek Saleh - Academia.edu (original) (raw)

Papers by Tarek Saleh

Research paper thumbnail of The role of neuropeptides and neurohormones in neurogenic cardiac arrhythmias

Current drug targets. Cardiovascular & haematological disorders, 2003

The functional significance of neuropeptides and neurohormones throughout the neuroaxis has been ... more The functional significance of neuropeptides and neurohormones throughout the neuroaxis has been the focus of considerable research over the past 25 years. These "gut peptides" or "reproductive hormones" have been localized within nuclei responsible for the relay of visceral afferent information to the forebrain. The presence of peptides and hormones along the gut- or heart-brain continuum suggests that these neurochemicals do more than modulate the visceral processes of digestion and reproduction respectively. Numerous studies have shown that the exogenous administration of these neurochemicals directly into visceral afferent nuclei significantly alters blood pressure, heart rate, autonomic tone and the sensitivity of the baroreceptor reflex (an index of sympatho-vagal balance). A strong inverse correlation has been demonstrated between the sensitivity of the baroreceptor reflex and susceptibility to lethal cardiac arrhythmias which lead ultimately to sudden car...

Research paper thumbnail of Estrogen not uncoupling protein-2 (UCP-2) alters the development of autonomic dysreflexia in mice

Research paper thumbnail of Visceral afferent stimulation-evoked changes in the release of peptides into the parabrachial nucleus in vivo

Brain Research, 1997

Previous investigations have demonstrated that the peptides substance P (SP), calcitonin gene-rel... more Previous investigations have demonstrated that the peptides substance P (SP), calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neurotensin (NT) and somatostatin (SOM) significantly modulate the glutamate-mediated transmission of visceral information through the parabrachial nucleus (PBN) to the ventrobasal thalamus. In addition, we have shown that the staining intensity of SOM, CCK and NT in the PBN decreases significantly following 2 h of vagal stimulation as visualized using immunohistochemistry. As well, the staining intensity of both SP and CGRP in the PBN were shown to increase under similar conditions. The present investigation was done to determine whether the altered peptide staining intensity of these peptides observed following 2 h of vagal stimulation was the result of an altered peptide release from terminals within the PBN. Male Sprague-Dawley rats were anesthetized with sodium thiobutabarbitol and instrumented to record blood pressure and heart rate and for the stimulation of the cervical vagus nerve. A push-pull perfusion cannula was lowered into the region of the PBN for the continuous sampling of extracellular fluid. Radioenzymatic quantification of the perfusates for peptide content revealed that the extracellular fluid concentration of CGRP and SP increased significantly during the 2 h of vagal stimulation. When the vagal stimulation was terminated, the release of both CGRP and SP decreased significantly below prestimulated values for approximately 30 min before returning to prestimulated levels shortly thereafter. In contrast, there was a significant decrease in the release of CCK, SOM and NT into the PBN during the period of vagal stimulation. Extracellular perfusate levels of these peptides returned to normal upon termination of stimulation. These results demonstrate that terminal release of CGRP and SP is significantly increased and terminal release of CCK, SOM and NT is significantly decreased in the PBN during 2 h of vagal stimulation. These results are consistent with our previous finding that the immunohistochemical staining intensity of CGRP and SP is increased while that of CCK, SOM and NT is decreased following vagal stimulation.

Research paper thumbnail of Estrogen reduces the severity of autonomic dysfunction in spinal cord-injured male mice

Behavioural Brain Research, 2006

Research paper thumbnail of Relaxin Pretreatment Decreases Infarct Size in Male Rats after Middle Cerebral Artery Occlusion

Annals of the New York Academy of Sciences, 2005

Research paper thumbnail of Suckerfish-ORD Menu

Research paper thumbnail of Neurotransmission of Visceral Information in the Parabrachial Nucleus of the Rat

Research paper thumbnail of Role of Oestrogen in the Central Regulation of Autonomic Function

Clinical and Experimental Pharmacology and Physiology, Sep 1, 2007

Research paper thumbnail of Partial Cranial Nerve III Palsy as a Manifestation of Undiagnosed Diabetes

Southern Medical Journal, Mar 1, 2010

... Monica Nicola, MD. Khushal Afzal, MD. Sheryl Dimayuga, MD. Department of Internal Medicine. S... more ... Monica Nicola, MD. Khushal Afzal, MD. Sheryl Dimayuga, MD. Department of Internal Medicine. Saint Joseph Mercy-Oakland. Pontiac, MI. ... Harrison's Principles of Internal Medicine. New York,McGraw-Hill, 2008, ed 17, pp 2657. Cited Here... 4. Jeganathan VS, Wang JJ, Wong TY ...

Research paper thumbnail of Neurochemical interactions in the para - brachial nucleus mediating visceral inputs to visceral thal

Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of vi... more Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of visceral information through the parabrachial nucleus (PBN) and that calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), neurotensin (NT), and cholecystokinin (CCK) may modulate these responses. The interactions of these neurotransmitters and neuropeptides were examined in male Wistar rats (17) that were anesthetized with chloral hydrate and ventilated and in which blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity of visceral thalamic neurons (VTNs). Peristimulus-time and continuous-time histograms of VTN activity were made before and after 200-nl injections of peptides, neurotransmitter agonists or antagonists, or artificial cerebrospinal fluid into the PBN. Combined injection of CGRP and SP into the PBN produced a synergistic inhibition of spontaneous VTN activity and the vagally evoked VTN response. Combined injection of NT and phenylephrine (PE) into the PBN produced only an additive increase in the spontaneous activity of VTNs. Prior administration of SOM in the PBN blocked the excitatory action of an alpha-adrenergic agonist (phenylephrine) injection on the spontaneous activity of VTNs, whereas CGRP, SP, or CCK had no effect on the alpha-agonist-induced response. Prior injection of an alpha-adrenergic antagonist (phentolamine) prevented the excitatory effect of NT in the PBN. Injection of CGRP, SP, NT, or CCK into the PBN did not change the response of VTNs to application of glutamate. These results suggest mechanisms for peptide interaction with primary neurotransmitters in the PBN and indicate whether the neuropeptides are acting before the primary neurotransmitter synapse or postsynaptically.

Research paper thumbnail of Reduction in infarct size by local estrogen does not prevent autonomic dysfunction after stroke

American Journal of Physiology Regulatory Integrative and Comparative Physiology, Dec 1, 2001

Research paper thumbnail of Abstract P211: Effect of Quality Improvement Discharge Tool in Heart Failure

Circulation Cardiovascular Quality and Outcomes, Nov 1, 2011

Research paper thumbnail of In Vitro Model of Focal Ischemia

Research paper thumbnail of Neurochemical interactions in the parabrachial nucleus mediating visceral inputs to visceral thalamic neurons

American Journal of Physiology Regulatory Integrative and Comparative Physiology, Apr 1, 1995

Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of vi... more Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of visceral information through the parabrachial nucleus (PBN) and that calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), neurotensin (NT), and cholecystokinin (CCK) may modulate these responses. The interactions of these neurotransmitters and neuropeptides were examined in male Wistar rats (17) that were anesthetized with chloral hydrate and ventilated and in which blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity of visceral thalamic neurons (VTNs). Peristimulus-time and continuous-time histograms of VTN activity were made before and after 200-nl injections of peptides, neurotransmitter agonists or antagonists, or artificial cerebrospinal fluid into the PBN. Combined injection of CGRP and SP into the PBN produced a synergistic inhibition of spontaneous VTN activity and the vagally evoked VTN response. Combined injection of NT and phenylephrine (PE) into the PBN produced only an additive increase in the spontaneous activity of VTNs. Prior administration of SOM in the PBN blocked the excitatory action of an alpha-adrenergic agonist (phenylephrine) injection on the spontaneous activity of VTNs, whereas CGRP, SP, or CCK had no effect on the alpha-agonist-induced response. Prior injection of an alpha-adrenergic antagonist (phentolamine) prevented the excitatory effect of NT in the PBN. Injection of CGRP, SP, NT, or CCK into the PBN did not change the response of VTNs to application of glutamate. These results suggest mechanisms for peptide interaction with primary neurotransmitters in the PBN and indicate whether the neuropeptides are acting before the primary neurotransmitter synapse or postsynaptically.

Research paper thumbnail of Acute injection of 17β-estradiol enhances cardiovascular reflexes and autonomic tone in ovariectomized female rats

Autonomic Neuroscience Basic Clinical, Oct 30, 2000

Research paper thumbnail of Role of 17β-estradiol in the modulation of baroreflex sensitivity in male rats

American Journal of Physiology Regulatory Integrative and Comparative Physiology, 1998

... stimulation. In conclusion, intravenous injection of estrogen in male rats significantly enha... more ... stimulation. In conclusion, intravenous injection of estrogen in male rats significantly enhanced baroreflex sensitivity and blocked the attenuation in the baroreflex sensitivity observed after vagal stimulation. ... 4). Vagal stimulation. ...

Research paper thumbnail of Peptidergic Modulation of Synaptic Transmission in the Parabrachial Nucleus In Vitro: Importance of Degradative Enzymes in Regulating Synaptic Efficacy

The Journal of Neuroscience the Official Journal of the Society For Neuroscience, Oct 1, 1996

Research paper thumbnail of Estrogen attenuates neuronal excitability in the insular cortex following middle cerebral artery occlusion

Brain Research, Aug 20, 2004

Research paper thumbnail of 17�-Estradiol release in the parabrachial nucleus of the rat evoked by visceral afferent activation

Mol Cell Endocrinol, 2002

In the present investigation, in vivo microdialysis was used to measure the concentration of estr... more In the present investigation, in vivo microdialysis was used to measure the concentration of estrogen in the parabrachial nucleus (PBN) and plasma of male and ovariectomized female Sprague–Dawley rats supplemented with either estrogen (OVX-E2) or saline (OVX-S) following visceral afferent activation. Analysis of dialysate samples prior to vagal stimulation and in non-stimulated controls revealed a continuous concentration of estrogen in the PBN for all treatment groups (male, 38±4 pg ml−1; OVX-E2, 38±5 pg ml−1; OVX-S, 33±4 pg ml−1). This concentration of estrogen in the PBN was significantly increased during vagal stimulation in all groups (male, 64±4 pg ml−1; OVX-E2, 104±9 pg ml−1; OVX-S, 80±6 pg ml−1; P<0.05) and returned to pre-stimulation values within 2 h following termination of the stimulation. Immunohistochemical analysis revealed that estrogen receptor (ERα and ERβ) density in males and ovariectomized saline-replaced female rats was significantly lower than that of estrogen-replaced female rats. These results suggest that estrogen is released into the PBN by an increase in visceral afferent traffic, however, alterations in estrogen receptor populations in the PBN may contribute to an attenuated physiological role of estrogen in the PBN of male and saline-replaced ovariectomized female rats.

Research paper thumbnail of Estrogen-induced autonomic effects are mediated by NMDA and GABAA receptors in the parabrachial nucleus

Research paper thumbnail of The role of neuropeptides and neurohormones in neurogenic cardiac arrhythmias

Current drug targets. Cardiovascular & haematological disorders, 2003

The functional significance of neuropeptides and neurohormones throughout the neuroaxis has been ... more The functional significance of neuropeptides and neurohormones throughout the neuroaxis has been the focus of considerable research over the past 25 years. These "gut peptides" or "reproductive hormones" have been localized within nuclei responsible for the relay of visceral afferent information to the forebrain. The presence of peptides and hormones along the gut- or heart-brain continuum suggests that these neurochemicals do more than modulate the visceral processes of digestion and reproduction respectively. Numerous studies have shown that the exogenous administration of these neurochemicals directly into visceral afferent nuclei significantly alters blood pressure, heart rate, autonomic tone and the sensitivity of the baroreceptor reflex (an index of sympatho-vagal balance). A strong inverse correlation has been demonstrated between the sensitivity of the baroreceptor reflex and susceptibility to lethal cardiac arrhythmias which lead ultimately to sudden car...

Research paper thumbnail of Estrogen not uncoupling protein-2 (UCP-2) alters the development of autonomic dysreflexia in mice

Research paper thumbnail of Visceral afferent stimulation-evoked changes in the release of peptides into the parabrachial nucleus in vivo

Brain Research, 1997

Previous investigations have demonstrated that the peptides substance P (SP), calcitonin gene-rel... more Previous investigations have demonstrated that the peptides substance P (SP), calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neurotensin (NT) and somatostatin (SOM) significantly modulate the glutamate-mediated transmission of visceral information through the parabrachial nucleus (PBN) to the ventrobasal thalamus. In addition, we have shown that the staining intensity of SOM, CCK and NT in the PBN decreases significantly following 2 h of vagal stimulation as visualized using immunohistochemistry. As well, the staining intensity of both SP and CGRP in the PBN were shown to increase under similar conditions. The present investigation was done to determine whether the altered peptide staining intensity of these peptides observed following 2 h of vagal stimulation was the result of an altered peptide release from terminals within the PBN. Male Sprague-Dawley rats were anesthetized with sodium thiobutabarbitol and instrumented to record blood pressure and heart rate and for the stimulation of the cervical vagus nerve. A push-pull perfusion cannula was lowered into the region of the PBN for the continuous sampling of extracellular fluid. Radioenzymatic quantification of the perfusates for peptide content revealed that the extracellular fluid concentration of CGRP and SP increased significantly during the 2 h of vagal stimulation. When the vagal stimulation was terminated, the release of both CGRP and SP decreased significantly below prestimulated values for approximately 30 min before returning to prestimulated levels shortly thereafter. In contrast, there was a significant decrease in the release of CCK, SOM and NT into the PBN during the period of vagal stimulation. Extracellular perfusate levels of these peptides returned to normal upon termination of stimulation. These results demonstrate that terminal release of CGRP and SP is significantly increased and terminal release of CCK, SOM and NT is significantly decreased in the PBN during 2 h of vagal stimulation. These results are consistent with our previous finding that the immunohistochemical staining intensity of CGRP and SP is increased while that of CCK, SOM and NT is decreased following vagal stimulation.

Research paper thumbnail of Estrogen reduces the severity of autonomic dysfunction in spinal cord-injured male mice

Behavioural Brain Research, 2006

Research paper thumbnail of Relaxin Pretreatment Decreases Infarct Size in Male Rats after Middle Cerebral Artery Occlusion

Annals of the New York Academy of Sciences, 2005

Research paper thumbnail of Suckerfish-ORD Menu

Research paper thumbnail of Neurotransmission of Visceral Information in the Parabrachial Nucleus of the Rat

Research paper thumbnail of Role of Oestrogen in the Central Regulation of Autonomic Function

Clinical and Experimental Pharmacology and Physiology, Sep 1, 2007

Research paper thumbnail of Partial Cranial Nerve III Palsy as a Manifestation of Undiagnosed Diabetes

Southern Medical Journal, Mar 1, 2010

... Monica Nicola, MD. Khushal Afzal, MD. Sheryl Dimayuga, MD. Department of Internal Medicine. S... more ... Monica Nicola, MD. Khushal Afzal, MD. Sheryl Dimayuga, MD. Department of Internal Medicine. Saint Joseph Mercy-Oakland. Pontiac, MI. ... Harrison's Principles of Internal Medicine. New York,McGraw-Hill, 2008, ed 17, pp 2657. Cited Here... 4. Jeganathan VS, Wang JJ, Wong TY ...

Research paper thumbnail of Neurochemical interactions in the para - brachial nucleus mediating visceral inputs to visceral thal

Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of vi... more Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of visceral information through the parabrachial nucleus (PBN) and that calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), neurotensin (NT), and cholecystokinin (CCK) may modulate these responses. The interactions of these neurotransmitters and neuropeptides were examined in male Wistar rats (17) that were anesthetized with chloral hydrate and ventilated and in which blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity of visceral thalamic neurons (VTNs). Peristimulus-time and continuous-time histograms of VTN activity were made before and after 200-nl injections of peptides, neurotransmitter agonists or antagonists, or artificial cerebrospinal fluid into the PBN. Combined injection of CGRP and SP into the PBN produced a synergistic inhibition of spontaneous VTN activity and the vagally evoked VTN response. Combined injection of NT and phenylephrine (PE) into the PBN produced only an additive increase in the spontaneous activity of VTNs. Prior administration of SOM in the PBN blocked the excitatory action of an alpha-adrenergic agonist (phenylephrine) injection on the spontaneous activity of VTNs, whereas CGRP, SP, or CCK had no effect on the alpha-agonist-induced response. Prior injection of an alpha-adrenergic antagonist (phentolamine) prevented the excitatory effect of NT in the PBN. Injection of CGRP, SP, NT, or CCK into the PBN did not change the response of VTNs to application of glutamate. These results suggest mechanisms for peptide interaction with primary neurotransmitters in the PBN and indicate whether the neuropeptides are acting before the primary neurotransmitter synapse or postsynaptically.

Research paper thumbnail of Reduction in infarct size by local estrogen does not prevent autonomic dysfunction after stroke

American Journal of Physiology Regulatory Integrative and Comparative Physiology, Dec 1, 2001

Research paper thumbnail of Abstract P211: Effect of Quality Improvement Discharge Tool in Heart Failure

Circulation Cardiovascular Quality and Outcomes, Nov 1, 2011

Research paper thumbnail of In Vitro Model of Focal Ischemia

Research paper thumbnail of Neurochemical interactions in the parabrachial nucleus mediating visceral inputs to visceral thalamic neurons

American Journal of Physiology Regulatory Integrative and Comparative Physiology, Apr 1, 1995

Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of vi... more Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of visceral information through the parabrachial nucleus (PBN) and that calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), neurotensin (NT), and cholecystokinin (CCK) may modulate these responses. The interactions of these neurotransmitters and neuropeptides were examined in male Wistar rats (17) that were anesthetized with chloral hydrate and ventilated and in which blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity of visceral thalamic neurons (VTNs). Peristimulus-time and continuous-time histograms of VTN activity were made before and after 200-nl injections of peptides, neurotransmitter agonists or antagonists, or artificial cerebrospinal fluid into the PBN. Combined injection of CGRP and SP into the PBN produced a synergistic inhibition of spontaneous VTN activity and the vagally evoked VTN response. Combined injection of NT and phenylephrine (PE) into the PBN produced only an additive increase in the spontaneous activity of VTNs. Prior administration of SOM in the PBN blocked the excitatory action of an alpha-adrenergic agonist (phenylephrine) injection on the spontaneous activity of VTNs, whereas CGRP, SP, or CCK had no effect on the alpha-agonist-induced response. Prior injection of an alpha-adrenergic antagonist (phentolamine) prevented the excitatory effect of NT in the PBN. Injection of CGRP, SP, NT, or CCK into the PBN did not change the response of VTNs to application of glutamate. These results suggest mechanisms for peptide interaction with primary neurotransmitters in the PBN and indicate whether the neuropeptides are acting before the primary neurotransmitter synapse or postsynaptically.

Research paper thumbnail of Acute injection of 17β-estradiol enhances cardiovascular reflexes and autonomic tone in ovariectomized female rats

Autonomic Neuroscience Basic Clinical, Oct 30, 2000

Research paper thumbnail of Role of 17β-estradiol in the modulation of baroreflex sensitivity in male rats

American Journal of Physiology Regulatory Integrative and Comparative Physiology, 1998

... stimulation. In conclusion, intravenous injection of estrogen in male rats significantly enha... more ... stimulation. In conclusion, intravenous injection of estrogen in male rats significantly enhanced baroreflex sensitivity and blocked the attenuation in the baroreflex sensitivity observed after vagal stimulation. ... 4). Vagal stimulation. ...

Research paper thumbnail of Peptidergic Modulation of Synaptic Transmission in the Parabrachial Nucleus In Vitro: Importance of Degradative Enzymes in Regulating Synaptic Efficacy

The Journal of Neuroscience the Official Journal of the Society For Neuroscience, Oct 1, 1996

Research paper thumbnail of Estrogen attenuates neuronal excitability in the insular cortex following middle cerebral artery occlusion

Brain Research, Aug 20, 2004

Research paper thumbnail of 17�-Estradiol release in the parabrachial nucleus of the rat evoked by visceral afferent activation

Mol Cell Endocrinol, 2002

In the present investigation, in vivo microdialysis was used to measure the concentration of estr... more In the present investigation, in vivo microdialysis was used to measure the concentration of estrogen in the parabrachial nucleus (PBN) and plasma of male and ovariectomized female Sprague–Dawley rats supplemented with either estrogen (OVX-E2) or saline (OVX-S) following visceral afferent activation. Analysis of dialysate samples prior to vagal stimulation and in non-stimulated controls revealed a continuous concentration of estrogen in the PBN for all treatment groups (male, 38±4 pg ml−1; OVX-E2, 38±5 pg ml−1; OVX-S, 33±4 pg ml−1). This concentration of estrogen in the PBN was significantly increased during vagal stimulation in all groups (male, 64±4 pg ml−1; OVX-E2, 104±9 pg ml−1; OVX-S, 80±6 pg ml−1; P<0.05) and returned to pre-stimulation values within 2 h following termination of the stimulation. Immunohistochemical analysis revealed that estrogen receptor (ERα and ERβ) density in males and ovariectomized saline-replaced female rats was significantly lower than that of estrogen-replaced female rats. These results suggest that estrogen is released into the PBN by an increase in visceral afferent traffic, however, alterations in estrogen receptor populations in the PBN may contribute to an attenuated physiological role of estrogen in the PBN of male and saline-replaced ovariectomized female rats.

Research paper thumbnail of Estrogen-induced autonomic effects are mediated by NMDA and GABAA receptors in the parabrachial nucleus