Prevention of isolation-induced hypertension by intrahippocampal administration of a nonpeptide kappa-opioid receptor agonist.

Previous research in this laboratory showed that hypertension in the spontaneous hypertensive rat (SHR) appears to correlate to insufficient production of hippocampal dynorphins, and that blood pressure could be reduced by intrahippocampal administration of dynorphins and nonpeptide kappa agonists. The purpose of the present study was to investigate whether kappa agonists could prevent the development of hypertension in a different hypertensive model, i.e., the isolated male rat model of hypertension (IHR). Isolation of young male rats for 5-7 days in standard rat cages caused an increase in systolic blood pressure from a mean of 132 to 184 mmHg. The blood pressures of rats grouped 3 per cage remained stable. Rats received the nonpeptide kappa agonist U62, 066E, (Spiradoline, Upjohn), 10 nmoles/0.2 microl or drug vehicle bilaterally into the the hippocampus for 3 days prior to and during isolation or grouping. Animals treated with U62, 066E did not develop hypertension as compared to isolated animals treated with vehicle. The isolation procedure used in these studies appears to induce anxietal stress, as indicated by reduced time spent by the rats in the open arms of the elevated-plus maze. This time is increased by U62, 066E, suggesting that the drug possesses anxiolytic properties and may reduce hypertension in part, by blocking an anxiety/stress component. These data strengthen our previous findings that opioids in the hippocampus may be important in restraining increased blood pressure provoked by environmental stimuli such as isolation.     

Changes in carotid flow velocity induced by lowering cerebrospinal fluid pressure in normal pressure hydrocephalus

Summary This is a report of changes in blood flow velocity in the carotid system induced by lumbar puncture in five patients who had clinical and neuroradiological signs of normal pressure hydrocephalus.After lowering cerebrospinal fluid pressure an increase of carotid flow velocity was found on Doppler hematotachography. These changes of carotid blood flow velocity could not be demonstrated in a control group of four patients with normal cerebrospinal fluid dynamics.This method is easy to perform, does not overtax the patient and seems to be indicated for the diagnosis of NPH. It is presented as a new, simple, reproducible aid to the diagnosis of NPH by Doppler hematotachography.

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Zusammenfassung Diese Präliminarstudie gibt eine Analyse der veränderten Blutstromgeschwindigkeit des Carotissystems nach einer Lumbalpunktion bei 5 Patienten, welche klinische und neurologische Symptome eines Hydrocephalus mit normalem Liquordruck zeigten.Nach Drucksenkung der Zerebrospinalflüssigkeit zeigte sich auf der Doppler-Hämatotachographie eine schnellere Durchströmung der Halsschlagader. In einer Kontrollgruppe von 4 Patienten mit normaler Dynamik der Zerebrospinalflüssigkeit konnten die Änderungen in der Blutdurchströmung der Halsschlagader nicht nachgewiesen werden.Die Durchführung dieser Methode ist einfach, sie beansprucht den Patienten nicht allzusehr und scheint indiziert für die Erkennung des Hydrocephalus mit normalem Druck.

     

Inhibitory effect of electroacupuncture (EA) on the pressor response induced by exercise stress

Abstract. We examined the effect of EA on the exercise stress-induced pressor response in healthy adult subjects of both sexes. Each subject was subjected to a bicycle exercise test using a ramp protocol once/week for three or four weeks. Subjects were asked to perform the following tests in random order: 1) a baseline exercise test without EA and 2) exercise after acupuncture at P 5–6, LI 4-L 7 and/or G 37–39 acupoints. Brachial systolic (SBP), diastolic (DBP), and mean blood pressures (MBP), heart rate (HR) and the rate-pressure product (RPP, systolic BP x HR/100) were measured every three min, while a 12 lead ECG was monitored continuously. We observed increases in MBP, SBP, HR and RPP in all 17 subjects during exercise. In 12 of the 17 subjects (71 %), EA for 30 min before exercise, either at Jianshi-Neiguan acupoints (P 5–6) or Hegu-Lique acupoints (LI 4-L 7), led to an increase in maximal workload, and reduced peak SBP, MBP and RPP responses to exercise; EA did not alter DBP or HR responses in these subjects. EA at control acupoints (Guangming-Xuanzhong acupoints, G 37–39) in five subjects did not alter the hemodynamic responses. Seven additional subjects were enrolled to study the effect of EA during a bicycle exercise test using a constant workload. The results were similar, in five of the seven subjects SBP, MBP and RPP after exercise were attenuated significantly by EA at P 5–6. We conclude that EA at specific acupoints improves exercise capacity and reduces the hemodynamic responses in approximately 70% of normal subjects.This project is supported by the DANA Foundation, the Susan-Sameuli Center for Integrative Medicine at UCI, the Larry K. Dodge Chair in Integrative Biology (JCL), and the General Clinical Research Center of UCI (5M61RR000827).     

Anatomical evidence that hypertension associated with the defence reaction in the cat is mediated by a direct projection from a restricted portion of the midbrain periaqueductal grey to the subretrofacial nucleus of the medulla

Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections were made at sites within a restricted portion of the midbrain periaqueductal grey region (PAG) of the cat at which microinjection of the excitant amino acid, d,l-homocysteic acid, elicits the strongest form of a defence reaction, including a hypertensive response. Among the revealed projections, significant anterograde labelling was found in a discrete region of the rostral ventrolateral medulla, the subretrofacial nucleus (SRF). In the cat, the SRF contains pressor neurones which project to the spinal preganglionic sympathetic outflow. The labelling was most marked ipsilaterally, although substantial contralateral labelling was also observed. To verify that the projection to the SRF originated from the restricted ‘defence region’ of the PAG, WGA-HRP or rhodamine-labelled microspheres were injected into physiologically-identified sites in the SRF. In all experiments, labelled neurones were found in the same restricted region of the PAG at which DLH injection evokes hypertension and behavioural signs of the defence reaction. The results are consistent with the hypothesis that a discrete cell group within the PAG mediates both somatic and autonomic components of the defence reaction and that the characteristic hypertensive response is mediated by a direct pathway from these PAG cells to pressor neurones in the SRF.     

"Obtundation Status (Dravet)" Caused by Complex Partial Status Epilepticus in a Patient with Severe Myoclonic Epilepsy in Infancy

Summary: Purpose : We report a 1-year 7-month-old boy with severe myoclonic epilepsy in infancy (SME) who exhibited complex partial status epilepticus (CPSE), which was confirmed by ictal video-EEG analysis. This boy first had a hemi-convulsion in a hot bath at age 3 months. Thereafter, he exhibited both partial and generalized seizures that were extremely intractable. At age 9 months, he had a prolonged episode of impaired consciousness that fit the "obtundation status in SME" defined by Dravet et al.
Methods and Results : Ictal EEG revealed persisting irregular spike-and-wave complexes over the left hemisphere, predominantly in the occipitotemporal area, and confirmed CPSE. The EEG abnormalities with decreased level of the consciousness continued -6 h after onset of the symptoms even with AED administration.
Conclusions : Because SME features both generalized and focal seizures, both types of nonconvulsive status may be seen in SME. Although Dravet et al. already reported long-lasting atypical absences in patients with SME as "obtundation status," we demonstrated CPSE in an infant with SME who exhibited a prolonged stuporous state.     

Water response of frog olfactory system is induced by a decrease in osmotic pressure

The frog olfactory response to deionized water (water response) was recorded from the olfactory bulb. The water response was suppressed by both electrolytes and non-electrolytes as a function of osmolarity, while the water response in taste cell was not suppressed by non-electrolytes. It was concluded that a decrease in osmotic pressure induced by application of deionized water is the origin of the water response in the frog olfactory system.     

Cardiovascular and behavioural effects induced by naloxone-precipitated morphine withdrawal in rat: characterization with tachykinin antagonists

This study examined the intracerebroventricular (i.c.v.) effects of three selective tachykinin receptor antagonists on the cardiovascular and behavioural responses induced by naloxone-precipitated morphine withdrawal in rats. I.c.v. injection of naloxone (10 microg) to morphine pre-treated rats (i.c.v. for 5 days) induced an immediate increase in blood pressure ( approximately 10 mmHg) and behavioural activity (sniffing > rearing > face washing approximately grooming approximately wet dog shake) without causing significant heart rate changes. The prior i.c.v. injection of the NK(1) receptor antagonist (6.5 nmol LY306740) reduced face washing and grooming during morphine withdrawal. NK(2) and NK(3) receptor antagonists (6.5 nmol SR48968 and R820) did not affect behavioural effects, yet the co-injection of the three tachykinin antagonists reduced all behavioural activity. The pressor response was not affected by the selective inhibition of NK(1) and NK(3) receptors while both blood pressure and heart rate were markedly enhanced by SR48968 during morphine withdrawal. The potentiating effect of SR48968 was prevented following simultaneous blockade of the three tachykinin receptors. In addition to confirming the involvement of central tachykinins in behavioural manifestations to morphine withdrawal, data suggest a modulatory function for tachykinins, especially the NK(2) receptor, in brain autonomic control of blood pressure and heart rate in supraspinal noloxone-precipitated withdrawal.     

Sensitization of the nervous system, induced by two successive hindpaw inflammations, is suppressed by a local anesthetic

Two hindpaw injections of carrageenin were performed 7 days apart and the time-course of the vocalization thresholds to pressure (VTPP) of all the 4 paws of the rat were measured after both injections. The first injection of carrageenin induced an increase in the circumference of the injected paw and a significant reduction of the VTPPs of all the 4 paws. The pain-related behavior of both hindpaws was enhanced, when carrageenin was injected for the second time not only into the previously inflamed, but also into the contralateral hindpaw. However, the abnormal responses of the forepaws were not increased by this second hindpaw inflammation. Both after the first and the second injection of carrageenin, the decrease of the VTPPs of all 4 paws was antagonized by lidocaine with epinephrine (LE) injected into the inflamed paw. This anesthetic effect was of a shorter duration after the second than after the first injection of carrageenin. Presumably, the imprint that is left in the nervous system after the first hindpaw inflammation, takes place at a relatively limited segmental level. In addition, it is possible to influence the established sensitization of the nervous system by treating the peripheral process itself, even when the first injury has primed the nervous system to the second injury. However, there still seems to exist some excitatory influences that cannot be suppressed by the local anesthetic.     

Treatment of refractory intracranial hypertension in a spina bifida patient by a concurrent ventricular and cisterna magna-to-peritoneal shunt

Case report A 20-year-old female born with a thoracic level myelomeningocele, Chiari II malformation, and hydrocephalus treated at birth developed clinical features of increased intracranial pressure (ICP) due to shunt malfunction. The patient became comatose. Her ICP remained high despite a functioning shunt and even after the ventricular catheter was exteriorized. Diagnostic imaging consistently demonstrated slit-like ventricles, a Chiari II malformation, and a tethered spinal cord. We attributed her neurological condition either to brainstem compression or increased ICP related to venous outlet obstruction at the foramen magnum.Outcome The patient improved rapidly after undergoing a Chiari II decompression and placement of a shunt from the cisterna magna and upper cervical subarachnoid space to the peritoneum connected by a Y connector to the ventricular catheter.Conclusion The complex hydrocephalus was effectively treated by this concurrent ventricular and cisterna magna-to-peritoneum shunt.     

In vivo influence of ceramide accumulation induced by treatment with a glucosylceramide synthase inhibitor on ischemic neuronal cell death

It has been shown that exogenous ceramide induces delayed neuronal death (DND) of cultured hippocampal neurons. To evaluate the role of endogenous ceramide in ischemic DND, the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), was used to generate ceramide in gerbil hippocampi in vivo. The trimethylsilylated derivatives of ceramide were analyzed directly by gas chromatography mass spectrometry, after separation with high-performance thin-layer chromatography. The ceramide compositions in vehicle hippocampus consisted mainly of C18:0 fatty acyl sphingosine (87.9%), with C16:0 and C20:0 ceramides being minor components (7.1% and 5.1%, respectively). Ceramide level in the hippocampi from gerbils subjected to D-PDMP treatment was 1.5-fold higher than those from vehicle-treated gerbils. In spite of the accumulation of ceramide observed in the D-PDMP group, the histological studies did not reveal any ischemic neuronal death in hippocampal CA1 neurons with the gerbils that had been subjected to a sham operation (2-min sublethal ischemia). These results suggest that the ceramide accumulation induced by blocking the de novo synthesis of glucosylceramide with D-PDMP may be independent of the metabolic pathway underlying ischemic DND.     

Intracranial hypertension caused by superior sagittal sinus stenosis secondary to a depressed skull fracture: Case report and review of the literature

Depressed fractures that occur on the superior sagittal sinus (SSS) cause stenosis or thrombosis of the sinus in 11.5% of cases. Despite this, the appearance of signs and symptoms derived from high intracranial pressure is an infrequent event. So far, only 17 cases of venous sinus injury causing intracranial hypertension have been documented. It is necessary to establish treatment immediately before clinical suspicion. Surgical treatment by craniectomy is a fast, effective and safe alternative according to the series. However, it is necessary to anticipate the possibility of haemorrhage in the operating room.The case of a 7-year-old girl admitted for traumatic brain injury (TBI) with the diagnosis of a left parasagittal occipital sinus fracture that stenosed the posterior third of the superior sagittal sinus is presented. Upon arrival, she was asymptomatic, and conservative management was selected. Subsequently, the patient began to present with headache, nausea, vomiting and diplopia associated with bradycardia and apnoea pauses of central origin. She underwent surgery with a craniectomy with satisfactory clinical and radiological evolution and normalization of the intracranial pressure (ICP) registry.