The Effect of α-Adrenergic Receptor Blockers Prazosin and Yohimbine on Cerebral Metabolism and Biogenic Amine Content of Traumatized Brain

Widespread decrease in local cerebral glucose utilization (LCGU) previously shown to occur 3 days after a focal freezing lesion was interpreted as reflecting a depression of functional activity in the affected areas. In parallel experiments, cortical norepinephrine (NE) content of traumatized brain was found to be decreased. The effects of prazosin (PZ), an α1-adrenergic receptor blocker, and yohimbine (YOH), an α2-blocker, on glucose use and biogenic amine content of lesioned rat brain were studied to determine if the changes in the noradrenergic system associated with injury are of functional importance, to identify the receptors that may be involved in mediating the action of NE in injured brain, and to look for evidence of interaction between the noradrenergic and the serotonergic systems in traumatized brain. PZ (1 mg/kg) given 30 min before the lesion ameliorated the subsequent metabolic cortical depression seen in untreated animals. PZ given for 3 days starting before the lesion (3 mg/kg/day) was also effective in normalizing LCGU in areas where it was depressed by lesioning, despite the fact that this regimen induced significant global decrease in LCGU in normal animals. Once cortical metabolic depression had developed 3 days after the lesion, it could not be modified by PZ. YOH was less effective than PZ and was so only when given for 3 days (22.5 mg/kg/day in three divided doses). PZ (3 mg/kg/day in three divided doses) slightly but significantly decreased the accumulation of the serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid in the traumatized hemisphere. These results provide evidence that blockage of α1adrenergic receptors prevents the development of cortical dysfunction associated with brain trauma. This implies that the noradrenergic system plays a role in the functional consequences of injury and that this effect is, at least in part, mediated by α1-adrenergic receptors. Furthermore, α1-adrenergic receptor blockage appears to modulate cortical turnover of 5-HT, previously also implicated in functional consequences of brain injury. The data are compatible with inhibitory effects of NE in the cortex and suggest a potential of α1-adrenergic blockage in development of novel therapeutic approaches to brain injury.

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The Effect of p-Chlorophenylalanine on Cerebral Metabolism and Biogenic Amine Content of Traumatized Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1988.67 ◽

1988 ◽

Vol 8 (3) ◽

pp. 324-334 ◽

Cited By ~ 51

Author(s):

Hanna M. Pappius ◽

Ralph Dadoun ◽

Michael McHugh

Keyword(s):

Biogenic Amine ◽

Glucose Utilization ◽

Cerebral Metabolism ◽

Serotonergic System ◽

Dependent Manner ◽

Injured Brain ◽

Amine Content ◽

Intact Brain ◽

Hydroxyindoleacetic Acid

It was shown previously that focal cortical freezing lesions in rats cause widespread decrease in local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere. This was interpreted as reflecting a depression of cortical activity. It was then demonstrated that cortical serotonin (5-HT) metabolism was increased throughout the lesioned hemisphere of a focally injured brain. To find out if the changes in the serotonergic system are of functional importance and mediate the observed changes in LCGU, the effects of the inhibition of 5-HT synthesis with p-chlorophenylalanine (PCPA) on cerebral metabolism and biogenic amine content in injured brain were studied. PCPA in doses up to 300 mg/kg had little, if any, effect on LCGU in intact brain and in doses up to 100 mg/kg did not modify the depressed LCGU in injured brain. In doses of 200 and 300 mg/kg, PCPA selectively increased cortical glucose utilization in the lesioned hemisphere where it was depressed following injury. PCPA decreased 5-HT levels in cortical and raphe areas of both intact and injured brain in a dose-dependent manner. However, at doses of PCPA ineffective on LCGU (50 and 100 mg/kg), traumatization still resulted in increased 5-HT metabolism. Doses of PCPA that ameliorated the depression of LCGU in injured brain completely prevented increases in both 5-HT and its metabolite 5-hydroxyindoleacetic acid seen following traumatization in untreated animals. These results provide evidence that decreased LCGU in lesioned brain is due to an activation of the serotonergic system by traumatization. The data are in agreement with the postulated inhibitory role of serotonin in the cortex and its involvement in functional alterations associated with injury. They suggest that blockage of this neurotransmitter system may have a potential in the development of novel therapeutic approaches to brain injury.

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Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIo Neurons by Presynaptic α2-Adrenergic Receptors

Journal of Neurophysiology ◽

10.1152/jn.00575.2001 ◽

2002 ◽

Vol 87 (4) ◽

pp. 1938-1947 ◽

Cited By ~ 86

Author(s):

Yu-Zhen Pan ◽

De-Pei Li ◽

Hui-Lin Pan

Keyword(s):

Receptor Antagonist ◽

Synaptic Input ◽

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Dorsal Root ◽

Primary Afferents ◽

Noradrenergic System ◽

Analgesic Action ◽

Adrenergic Agonists ◽

Excitatory Synaptic Input

Activation of spinal α2-adrenergic receptors by the descending noradrenergic system and α2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered α2-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina IIo) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic α2-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina IIo neurons. Whole cell voltage-clamp recordings were performed on visualized lamina IIo neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 μM) significantly decreased the frequency of mEPSCs from 5.8 ± 0.9 to 2.7 ± 0.6 Hz (means ± SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina IIo neurons. Yohimbine (2 μM, an α2-adrenergic receptor antagonist), but not prazosin (2 μM, an α1-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1–20 μM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine ( n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina IIo neurons through activation of α2-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina IIoneurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and α2-adrenergic agonists.

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Traumatic Brain Injury: A Trauma Surgeon's Perspective

Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders ◽

10.1044/nnsld22.3.82 ◽

2012 ◽

Vol 22 (3) ◽

pp. 82-89

Author(s):

Oscar D. Guillamondegui

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Multidisciplinary Approach ◽

Trauma Team ◽

The United States ◽

Long Term Outcomes ◽

Term Care ◽

Injured Brain ◽

The Moment

Traumatic brain injury (TBI) is a serious epidemic in the United States. It affects patients of all ages, race, and socioeconomic status (SES). The current care of these patients typically manifests after sequelae have been identified after discharge from the hospital, long after the inciting event. The purpose of this article is to introduce the concept of identification and management of the TBI patient from the moment of injury through long-term care as a multidisciplinary approach. By promoting an awareness of the issues that develop around the acutely injured brain and linking them to long-term outcomes, the trauma team can initiate care early to alter the effect on the patient, family, and community. Hopefully, by describing the care afforded at a trauma center and by a multidisciplinary team, we can bring a better understanding to the armamentarium of methods utilized to treat the difficult population of TBI patients.

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Faculty Opinions recommendation of Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1158503.618678 ◽

2009 ◽

Author(s):

Arun Gupta

Keyword(s):

Traumatic Brain Injury ◽

Blood Glucose ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Cerebral Metabolism ◽

Arterial Blood ◽

Arterial Blood Glucose

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Role of beta-adrenergic receptor subtypes in pig uterus contractility with inflammation

Scientific Reports ◽

10.1038/s41598-021-91184-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Barbara Jana ◽

Jarosław Całka

Keyword(s):

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Domestic Animals ◽

Inhibitory Effect ◽

Receptor Subtypes ◽

Beta Adrenergic Receptor ◽

Pharmacological Modulation ◽

Uterine Inflammation ◽

Myometrial Contractility

AbstractUterine inflammation is a very common and serious condition in domestic animals. To development and progression of this pathology often lead disturbances in myometrial contractility. Participation of β1-, β2- and β3-adrenergic receptors (ARs) in noradrenaline (NA)-influenced contractility of the pig inflamed uterus was studied. The gilts of SAL- and E.coli-treated groups were administered saline or E.coli suspension into the uterine horns, respectively. Laparotomy was only done in the CON group. Compared to the period before NA administration, this neurotransmitter reduced the tension, amplitude and frequency in uterine strips of the CON and SAL groups. In the E.coli group, NA decreased the amplitude and frequency, and these parameters were lower than in other groups. In the CON, SAL and E.coli groups, β1- and β3-ARs antagonists in more cases did not significantly change and partly eliminated NA inhibitory effect on amplitude and frequency, as compared to NA action alone. In turn, β2-ARs antagonist completely abolished NA relaxatory effect on these parameters in three groups. Summarizing, NA decreases the contractile amplitude and frequency of pig inflamed uterus via all β-ARs subtypes, however, β2-ARs have the greatest importance. Given this, pharmacological modulation of particular β-ARs subtypes can be used to increase inflamed uterus contractility.

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Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)53678-4 ◽

1993 ◽

Vol 268 (5) ◽

pp. 3201-3208

Author(s):

S. Pippig ◽

S. Andexinger ◽

K. Daniel ◽

M. Puzicha ◽

M.G. Caron ◽

...

Keyword(s):

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Receptor Kinase ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Beta 2

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125I-labeled p-azidobenzylcarazolol, a photoaffinity label for the beta-adrenergic receptor. Characterization of the ligand and photoaffinity labeling of beta 1- and beta 2-adrenergic receptors.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)33718-9 ◽

1982 ◽

Vol 257 (20) ◽

pp. 12332-12340 ◽

Cited By ~ 5

Author(s):

T N Lavin ◽

P Nambi ◽

S L Heald ◽

P W Jeffs ◽

R J Lefkowitz ◽

...

Keyword(s):

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Photoaffinity Labeling ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Photoaffinity Label ◽

Beta 2

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α-Adrenergic receptor modulation of the intrathoracic efferent sympathetic nervous system regulating the canine heart

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-190 ◽

1989 ◽

Vol 67 (10) ◽

pp. 1199-1204 ◽

Cited By ~ 2

Author(s):

J. A. Armour

Keyword(s):

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Blocking Agent ◽

Sympathetic Ganglia ◽

Canine Heart ◽

Receptor Modulation ◽

Adrenergic Antagonist ◽

Cervical Ganglia ◽

Β Adrenergic Receptors ◽

Stimulation Of

The augmentation of ventricular inotropism induced by electrical stimulation of acutely decentralized efferent sympathetic preganglionic axons was reduced, but still present, following administraiton of hexamethonium (10 mg/kg i.v.). While hexamethonium continued to be administered, the cardiac augmentations so induced were enhanced significantly following administration of the α-adrenergic receptor blocking agent, phentolamine myselate (1 mg/kg i.v.). Stimulation of the sympathetic efferent postganglionic axons in cardiopulmonary nerves induced cardiac augmentations that were unchanged following administration of these agents singly or together. The cardiac augmentations induced by stimulation of efferent preganglionic sympathetic axons were unchanged when phentolamine was administered alone. The augmentations of cardiac inotropism induced by efferent postganglionic sympathetic axonal stimulation were decreased following local administration of the β-adrenergic antagonist timolol into the ipsilateral stellate and middle cervical ganglia. Thereafter, these augmentations were unchanged following the subsequent intravenous administration of phentolamine. It is concluded that the activation of cardiac neurons in the stellate and middle cervical ganglia by stimulation of efferent preganglionic sympathetic axons can be modified by α-adrenergic receptors and that these effects are dependent upon β-adrenergic receptors, not nicotinic ones, in intrathoracic ganglia.Key words: α-adrenergic inotropism, sympathetic ganglia, hexamethonium, phentolamine.

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