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D F Hanley

Publications and source records attributed to D F Hanley.

At least 19 recordsLinked to original sources
PubMed1999

GABA- and glutamate-activated channels in green fluorescent protein-tagged gonadotropin-releasing hormone neurons in transgenic mice.

Mice were generated expressing green fluorescent protein (GFP) under the control of the gonadotropin-releasing hormone (GnRH) promoter. Green fluorescence was observed in, and restricted to, GnRH-immunopositive neuronal somata in the olfactory bulb, ganglion terminale, septal nuclei, diagonal band of Broca (DBB), preoptic area (POA), and caudal hypothalamus, as well as GnRH neuronal dendrites and axons, including axon terminals in the median eminence and organum vasculosum of the lamina terminalis (OVLT). Whole-cell recordings from GFP-expressing GnRH neurons in the OVLT-POA-DBB region revealed a firing pattern among GFP-expressing GnRH neurons distinct from that of nonfluorescent neurons. Nucleated patches of GFP-expressing GnRH neurons exhibited pronounced responses to fast application of GABA and smaller responses to L-glutamate and AMPA. One-fifth of the nucleated patches responded to NMDA. The GABA-A, AMPA, and NMDA receptor channels on GnRH neurons mediating these responses may play a role in the modulation of GnRH secretory oscillations.

Action Potentials↗
PubMed1999

Somatosensory stimulus entrains spindle oscillations in the thalamic VPL nucleus in barbiturate anesthetized rats.

This study reports the effect of external stimuli on spindle oscillations in the somatosensory thalamus of barbiturate anesthetized rats. Multi-unit responses to somatosensory stimuli were measured from the contralateral thalamic ventral posterior lateral (VPL) nucleus at different stimulus strengths and periods. Spindle oscillations could be entrained by the somatosensory stimuli at periods between 2 and 5 s. A resonance phenomenon described as a quiescent pre-stimulus period followed by entrained post-stimulus oscillations, was observed for somatosensory stimuli above the threshold for eliciting cortical evoked potentials and a stimulus period between 2 and 5 s. This study demonstrates an ascending pathway for localized modulation of spindle oscillations.

Anesthesia↗
PubMed1999

No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage.

OBJECTIVES: To determine the effect of massive intracerebral hemorrhage (ICH) on regional cerebral blood flow (rCBF) and metabolism, and to test the hypothesis that there is persistent ischemia in the perihematoma region after ICH. BACKGROUND: Cerebral ischemia is postulated to be one of the mechanisms of neural injury after ICH. Presumably the hematoma induces ischemia by mechanical compression of the surrounding microvasculature. METHODS: The authors induced ICH in eight anesthetized mongrel dogs by autologous blood injection (7.5 mL) under arterial pressure in the deep white matter adjacent to the left basal ganglia. They measured serial rCBF using radiolabeled microspheres in regions around and distant to the hematoma, as well as cerebral oxygen extraction, oxygen consumption (CMRO2), glucose utilization, and lactate production by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were monitored continuously. All measurements were recorded at 0.5, 1.0, 2.0, 3.5, and 5.0 hours after induction of ICH and compared with prehematoma values. Evans Blue dye was injected at the end of the experiment, and intensity of staining was compared with three control animals. RESULTS: Compared with prehematoma ICP (12.5+/-2.0 mm Hg, mean+/-standard error), significant elevation in ICP was observed after ICH peaking at 5 hours (34.4+/-5.2 mm Hg). Compared with prehematoma MAP (125.8+/-7.0 mm Hg), significant elevation in MAP was observed at 120 minutes after onset of hematoma (139.1+/-4.6 mm Hg), with return to the prehematoma value by 5 hours. There were no significant changes observed in cerebral oxygen extraction (51.4+/-4.3% versus 44.8+/-4.9%) and CMRO2 (1.8+/-0.3 versus 1.64+/-0.2 mL O2/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. There were no significant differences observed in rCBF in the perihematoma gray (18.2+/-0.9 mL/100 g/min versus 20.1+/-1.5 mL/100 g/min) or white matter (15.6+/-1.4 mL/100 g/min versus 15.3+/-1.1 mL/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. No changes were observed in cerebral glucose utilization, lactate production, and rCBF in other regions after introduction of ICH. Permeability of the blood-brain barrier was more prominent in the ipsilateral hemisphere in animals with ICH compared with control animals. CONCLUSIONS: Despite a prominent increase in ICP and MAP after ICH, the authors found no evidence to support the presence of an ischemic penumbra in the first 5 hours after ICH. Thus, other mechanisms for acute neural injury and late rCBF changes after ICH must be investigated.

Animals↗
PubMed1999

TCD, MRA and MRI in acute cerebral ischemia.

OBJECTIVES: The aim of this study was to determine accuracy of transcranial Doppler ultrasound (TCD) and compare efficacy of three non-invasive tests [TCD, magnetic resonance angiography (MRA), and magnetic resonance imaging (MRI)] in patients with acute cerebral ischemia. MATERIAL AND METHODS: This prospective study involved 30 patients. MRI, MRA, and TCD were performed within 24 h after onset of ictus. The 2nd MRI was repeated at 48-72 h and was used as the standard for the evaluation of sensitivity and specificity of MRA, TCD, and initial MRI. RESULTS: TCD showed a sensitivity of 96% and a specificity of 33% for recognizing abnormal cerebral blood flow velocities. MRA showed a sensitivity of 46% and a specificity of 75% for assessing intracranial vascular anatomy, while initial MRI revealed a sensitivity of 84% and a specificity of 100% for evaluation of ischemic parenchymal changes. CONCLUSION: Our results revealed that TCD is an accurate indicator of blood flow status and correlated well with MRI, MRA abnormalities in acute stroke.

Adult↗
PubMed1998

Nerve growth factor rapidly suppresses basal, NMDA-evoked, and AMPA-evoked nitric oxide synthase activity in rat hippocampus in vivo.

In adult forebrain, nerve growth factor (NGF) influences neuronal maintenance and axon sprouting and is neuroprotective in several injury models through mechanisms that are incompletely understood. Most NGF signaling is thought to occur after internalization and retrograde transport of trkA receptor and be mediated through the nucleus. However, NGF expression in hippocampus is rapidly and sensitively regulated by synaptic activity, suggesting that NGF exerts local effects more dynamically than possible through signaling requiring retrograde transport to distant afferent neurons. Interactions have been reported between NGF and nitric oxide (NO). Because NO affects both neural plasticity and degeneration, and trk receptors can mediate signaling within minutes, we hypothesized that NGF might rapidly modulate NO production. Using in vivo microdialysis we measured conversion of L-[14C]arginine to L-[14C]citrulline as an accurate reflection of NO synthase (NOS) activity in adult rat hippocampus. NGF significantly reduced NOS activity to 61% of basal levels within 20 min of onset of delivery and maintained NOS activity at less than 50% of baseline throughout 3 hr of delivery. This effect did not occur with control protein (cytochrome c) and was not mediated by an effect of NGF on glutamate levels. In addition, simultaneous delivery of NGF prevented significant increases in NOS activity triggered by the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Rapid suppression by NGF of basal and glutamate-stimulated NOS activity may regulate neuromodulatory functions of NO or protect neurons from NO toxicity and suggests a novel mechanism for rapidly mediating functions of NGF and other neurotrophins.

Animals↗
PubMed1998

Magnetic resonance imaging, unstable intracranial pressure and clinical outcome in patients with normal pressure hydrocephalus.

To identify features on magnetic resonance imaging (MRI) scans that are associated with unstable intracranial pressure (ICP) and outcome after CSF shunting in patients with NPH, we reviewed MRI scans of 17 patients who had continuous ICP monitoring performed prior to ventriculo-peritoneal shunt insertion. We evaluated the association between periventricular/deep white matter lesion burden, focal impingement of the corpus callosum, aqueductal CSF flow void, and B-waves with outcome after shunting. The change in neurological function between pre- and post CSF shunting evaluation was scored according to a standard scale (range -3 or +3). Patients were divided into those with clinical improvement (score > 0) or without improvement (score < or = 0) after shunt surgery. Focal impingement of the corpus callosum was more frequent in patients who improved after CSF shunting compared to those without improvement (8 of 13 vs 0 of 4, p = 0.05). Patients with focal impingement of corpus callosum had more B-wave time than those without impingement (60.5% vs 24.7%, p = 0.02). Focal impingement of corpus callosum on MRI may be associated with unstable intracranial pressure in patients with NPH and may be useful in identifying patients who will benefit from CSF shunting.

Aged↗
PubMed1998

Evaluation of shunt function in patients who are never better, or better than worse after shunt surgery for NPH.

We investigated the cause of poor outcome in patients with normal pressure hydrocephalus (NPH) who did not respond as expected after shunt surgery. Two methods were used to evaluate shunts: radionuclide shunt patency study, or continuous ICP monitoring. 33/52 shunted patients (64%) from 1989 to 1995 had poor outcome, and 28/52 (54%) were investigated. Of those investigated, 9/28 (32%) were never better, and 19/28 (68%) were initially better then worse. Of 9 patients who were never better, ineffective shunt function was seen in 7; 5 had shunt revision (2 declined), and 1 improved. Of 19 patients who were initially better then worse, 15 had ineffective shunts; 15 underwent shunt revision, and 13 improved. Poor clinical outcome occurred in two-thirds of all patients after shunt surgery for NPH, but a potentially treatable cause (i.e. obstruction of the shunt or a shunt system that was patent but did not adequately correct the CSF circulatory disorder) was found in nearly 80% (22/28) of those investigated. The predominant cause of ineffective shunt function was obstruction of the peritoneal catheter. Clinical recovery occurred in 70% (14/20) of patients who had shunt revision surgery. We conclude that ineffective shunt function is a frequent cause of poor outcome after shunt surgery to treat NPH that should be sought and treated. These results have implications for longitudinal studies of the diagnosis and treatment of NPH. The effect of unrecognized shunt ineffectiveness on prior studies is unknown. Future studies should be designed to confirm that shunts are functioning before the diagnosis of NPH is considered incorrect.

Cerebrospinal Fluid Shunts↗
PubMed1998

Comparison of Pcsf monitoring and controlled CSF drainage diagnose normal pressure hydrocephalus.

We evaluated 86 patients for possible normal pressure hydrocephalus (NPH) by: 1) CSF pressure (Pcsf) monitoring and analysis for percent of time with A or B-waves, and 2) controlled CSF drainage for 3 days via a lumbar subarachnoid catheter. Clinical outcome after CSF drainage and shunt surgery was assessed as change of clinical exam, with grades of none, minor, moderate, or marked change. For outcome analysis in 47 patients after shunt surgery, NPH was defined as moderate or marked clinical improvement. We assessed the diagnostic discrimination of percent-of-time thresholds of A and B-waves for 38 patients. At 10%, sensitivity for NPH is 91%, specificity is 13%, positive predictive value (PPV) is 62%, and the false positive rate is 38%. At the 25% threshold, sensitivity is 78%, specificity is 40%, PPV is 67%, false positive rate is 33%, and the false negative rate is 22%. For CSF drainage (threshold of minor improvement or better), the sensitivity is 97%, specificity is 60%, PPV is 84%, negative predictive value (NPV) is 90%, and the false negative rate is 3%. We conclude: 1) clinical response to controlled CSF drainage accurately predicts the outcome after shunt surgery in patients suspected of having NPH, and 2) A or B-waves poorly predict which patients will respond to shunt surgery. Three days of CSF drainage seems to encompass critical thresholds of CSF volume removal or duration of Pcsf reduction necessary for neuronal function to begin returning and symptoms to begin resolving in patients with NPH.

Catheters, Indwelling↗
PubMed1998

Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain.

OBJECTIVE: To determine the effect of continuous hypertonic (3%) saline/acetate infusion on intracranial pressure (ICP) and lateral displacement of the brain in patients with cerebral edema. DESIGN: Retrospective chart review. SETTINGS: Neurocritical care unit of a university hospital. PATIENTS: Twenty-seven consecutive patients with cerebral edema (30 episodes), including patients with head trauma (n = 8), postoperative edema (n = 5), nontraumatic intracranial hemorrhage (n = 8), and cerebral infarction (n = 6). INTERVENTION: Intravenous infusion of 3% saline/acetate to increase serum sodium concentrations to 145 to 155 mmol/L. MEASUREMENTS AND MAIN RESULTS: A reduction in mean ICP within the first 12 hrs correlating with an increase in the serum sodium concentration was observed in patients with head trauma (r2 = .91, p = .03), and postoperative edema (r2 = .82, p = .06), but not in patients with nontraumatic intracranial hemorrhage or cerebral infarction. In patients with head trauma, the beneficial effect of hypertonic saline on ICP was short-lasting, and after 72 hrs of infusion, four patients required intravenous pentobarbital due to poor ICP control. Among the 21 patients who had a repeat computed tomographic scan within 72 hrs of initiating hypertonic saline, lateral displacement of the brain was reduced in patients with head trauma (2.8 +/- 1.4 to 1.1 +/- 0.9 [SEM]) and in patients with postoperative edema (3.1 +/- 1.6 to 1.1 +/- 0.7). This effect was not observed in patients with nontraumatic intracranial bleeding or cerebral infarction. The treatment was terminated in three patients due to the development of pulmonary edema, and was terminated in another three patients due to development of diabetes insipidus. CONCLUSIONS: Hypertonic saline administration as a 3% infusion appears to be a promising therapy for cerebral edema in patients with head trauma or postoperative edema. Further studies are required to determine the optimal duration of benefit and the specific patient population that is most likely to benefit from this treatment.

Adult↗
PubMed1998

Treatment of refractory intracranial hypertension with 23.4% saline.

OBJECTIVE: To evaluate the effect of intravenous bolus administration of 23.4% saline (8008 mOsm/L) on refractory intracranial hypertension (RIH) in patients with diverse intracranial diseases. DESIGN: Retrospective chart review. SETTING: A neurosciences intensive care unit in a university hospital. PATIENTS: We present eight patients and a total of 20 episodes of increased intracranial pressure (ICP) resistant to standard modes of therapy. Five patients had subarachnoid hemorrhage, one patient had traumatic brain injury, one had a brain tumor, and another had spontaneous basal ganglia hemorrhage. Seven patients had intraventricular catheters, and one had a subarachnoid pressure screw placed. We monitored continuously mean ICP, serum sodium concentrations, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure, and urine output before and after the administration of hypertonic saline (HS). Post mortem examination of the brain was performed in two patients. INTERVENTION: Intravenous bolus administration of 30 mL of 23.4% saline. MEASUREMENTS AND MAIN RESULTS: There was a significant (p < .05) decrease in ICP from a median of 41.5 mm Hg before HS to 17 mm Hg at 1 hr, 16 mm Hg at 2 hrs, and 14 mm Hg at 3 hrs after HS administration. In 80% of cases, ICP decreased by >50% of the pretreatment value over a duration of 21.2+/-10.3 mins. ICP decreased to <20 mm Hg in 65% of all cases and the mean time for it to again exceed 20 mm Hg was 6.3+/-4.9 hrs. There was a significant improvement in CPP, from 64.7+/-19 (SD) mm Hg before HS to 85.6+/-18 mm Hg (1 hr) and 83+/-18 mm Hg (3 hrs) after HS. There were no significant differences in the other variables measured. The post mortem examinations showed no white matter changes or subdural collections. CONCLUSIONS: This preliminary case series suggests that the intravenous bolus administration of 23.4% saline reduces ICP and augments CPP in patients with resistant increased ICP. This reduction can be maintained for several hours while other therapeutic measures are being considered. The patient population most likely to respond to this therapy needs to be further defined. Although more research is needed, this treatment is promising as a new modality for RIH because of its ICP-lowering effect without intravascular volume depletion.

Adult↗
PubMed1998

Tyrosine confounds oxidative electrochemical detection of nitric oxide.

We report evidence that a porphyrinic microsensor for detection of nitric oxide (NO) also detects biologically relevant concentrations of tyrosine (Tyr) in dog brain. Tyr is oxidized by this sensor at the same potential as NO, and the sensitivity for NO and Tyr are of the same order of magnitude. The interference from Tyr is of importance because 1) Tyr is abundant and 2) there is a concentration gradient of Tyr across the blood-brain barrier that can lead to unpredictable results if disturbed by ischemia or hypoxia. The knowledge of this interference is important for the interpretation of results obtained with this sensor and for the design of future studies.

Animals↗
PubMed1997

Characterization of metabotropic glutamate receptor-mediated nitric oxide production in vivo.

We tested the hypothesis that stimulation of metabotropic glutamate receptors (mGluRs) increases nitric oxide (NO) production in the hippocampus in vivo. Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of adult Sprague-Dawley rats under pentobarbital anesthesia. Probes were perfused for 5 h with artificial cerebrospinal fluid (CSF) containing 3 microM [14C]-L-arginine. Recovery of [14C]-L-citrulline in the effluent was used as a marker of NO production. In nine groups of rats, increases in [14C]-L-citrulline recovery were compared between right- and left-sided probes perfused with various combinations of the selective mGluR agonist, trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD); the mGluR antagonist, (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG); the NO synthase inhibitor, N-nitro-L-arginine (LNNA); the ryanodine sensitive calcium-release channel inhibitor dantrolene, the non-N-methyl-D-aspartate (NMDA); receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801); and the Na+ channel blocker, tetrodotoxin. Recovery of [14C]-L-citrulline during perfusion with artificial CSF progressively increased to 90 +/- 21 fmol/min (+/-SD) over 5 h. Perfusion in the contralateral hippocampus with 1 mM ACPD augmented [14C]-L-citrulline recovery to 250 +/- 81 fmol/min. Perfusion of 1 mM nitroarginine + ACPD inhibited [14C]-L-citrulline recovery compared to that with ACPD alone. Perfusion with 1 mM MCPG + ACPD attenuated ACPD enhanced [14C]-L-citrulline recovery. Perfusion of 1 mM dantrolene + ACPD inhibited the ACPD-evoked increase in [14C]-L-citrulline recovery. Perfusion of 1 mM MCPG or dantrolene without ACPD did not decrease [14C]-L-citrulline recovery as compared to CSF alone. ACPD-enhanced [14C]-L-citrulline recovery was not attenuated by CNQX, MK-801, or tetrodotoxin (TTX). Using an indirect method of assessing NO production in vivo, these data demonstrate that mGluR stimulation enhances NO production in rat hippocampus. Inhibition with dantrolene suggests that calcium-induced calcium release amplifies the inositol triphosphate-mediated calcium signal associated with mGluR stimulation, thereby resulting in augmented calcium-dependent NO production.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

NO contributes to neurohypophysial but not other regional cerebral fluorocarbon-induced hyperemia in cats.

The large increase in cerebral blood flow (CBF) after fluorocarbon (FC)-exchange transfusion is thought to be caused by low oxygen content, decreased viscosity, or direct vasodilatory effect of the FC perfusate. The aim of this study was to determine whether nitric oxide (NO)-mediated vasorelaxation is increased in FC-perfused hemoglobin (Hb)-free cats because NO is not scavenged by Hb. We measured regional CBF with radiolabeled microspheres in three groups of anesthetized mechanically ventilated cats. The first group [FC + N(omega)-nitro-L-arginine methyl ester (L-NAME), n = 7] underwent a complete FC-exchange transfusion with FC-43 and subsequent nitric oxide synthase (NOS) inhibition with L-NAME (10 mg/kg i.v.) followed by L-arginine (100 mg/kg i.v.). A second group (FC + saline; n = 6) underwent an identical protocol, but NOS was not antagonized (saline i.v.). In a third group (blood + L-NAME; n = 7), cats were not FC exchanged but NOS was inhibited. In a separate cohort of four FC-perfused cats, NOS activity in brain tissue samples was reduced to 26% of control after NOS inhibition. FC-exchange transfusion nearly doubled hemispheric blood flow in both FC-exchanged groups, whereas it was constant in the blood + L-NAME group. These increases in regional CBF (hemispheres, brain stem, cerebellum, thalamus, and white matter) were not reversed by inhibition of NOS, except in the neurohypophysis, where L-NAME reduced blood flow to levels comparable to values in the blood + L-NAME group. In summary, increases in regional CBF after total FC-exchange transfusion are not caused by a lack of NO scavenging, with the exception of neurohypophysis. These findings suggest an increased vasorelaxation in neurohypophysis of FC-perfused and Hb-free cats caused by unscavenged NO, but this mechanism does not play a major role in FC-related CBF increases in the rest of the cerebral circulation.

Animals↗