Fractalkine signaling in microglia contributes to ectopic orofacial pain following trapezius muscle inflammation.

Fractalkine (FKN) signaling is involved in mechanical allodynia in the facial skin following trapezius muscle inflammation. Complete Freund's adjuvant (CFA) injection into the trapezius muscle produced mechanical allodynia in the ipsilateral facial skin that was not associated with facial skin inflammation and resulted in FKN but not FKN receptor (CX3CR1) expression, and microglial activation was enhanced in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). Intra-cisterna magna anti-CX3CR1 or anti-interleukin (IL)-1ß neutralizing antibody administration decreased the enhanced excitability of Vc and C1-C2 neurons in CFA-injected rats, whereas intra-cisterna magna FKN administration induced microglial activation and mechanical allodynia in the facial skin. IL-1ß expression and p38 mitogen-activated protein kinase phosphorylation were enhanced in activated microglia after CFA injection. The excitability of neurons whose receptive fields was located in the facial skin was significantly enhanced in CFA-injected rats, and the number of cells expressing phosphorylated extracellular signal-regulated kinase (pERK) following noxious mechanical stimulation of the facial skin was significantly increased in Vc and C1-C2. We also observed mechanical allodynia of the trapezius muscle as well as microglial activation and increased pERK expression in C2-C6 after noxious stimulation of the trapezius muscle in facial skin-inflamed rats. These findings suggest that FKN expression was enhanced in Vc and C1-C2 or C2-C6 following trapezius muscle or facial skin inflammation, microglia are activated via FKN signaling, IL-1ß is released from the activated microglia, and the excitability of neurons in Vc and C1-C2 or C2-C6 is enhanced, resulting in the ectopic mechanical allodynia.

The influence of cisternal and ventricular lavage on cerebral vasospasm in patients suffering from subarachnoid hemorrhage: analysis of effectiveness.

OBJECTIVE: within the last decades several clinical trials were performed to analyze the effectiveness of cisternal and ventricular lavage on cerebral vasospasm in patients suffering from subarachnoid hemorrhage. Aim of the present analysis was to review and summarize all documented clinical studies using cisternal or ventricular lavage to prevent vasospasm. METHODS: the MEDLINE Web site ( www.pub.med.com ) was searched using the clinical query function optimized for clinical therapy. Search terms were subarachnoid hemorrhage, vasospasm, cisternal and ventricular lavage. Results were divided into cisternal and ventricular lavage therapies alone and its combination with additional treatment modalities. RESULTS: so far the literature search revealed a total of nine clinical trials using cisternal or ventricular lavage alone in patients suffering from subarachnoid hemorrhage. The patients were treated using urokinase or recombinant tissue plasminogen activator. A metaanalysis, investigating a total of 652 included patients revealed a significant reduction of delayed neurological deficits, a significant increase of outcome and a significant decrease of mortality in the treatment group. Additional there was no difference of effectiveness or side effects using urokinase or recombinant tissue plasminogen activator. Hence, only one of these studies was based on a prospective, randomized study design. A combination of cisternal or ventricular lavage with some sort of kinetic treatment was documented in a total of three studies. All of them were designed prospectively. The combined application demonstrated reduced delayed neurological deficits, reduced vasospasm and better outcome in two studies for the treatment group. One study was stopped early due to unexpected complication. CONCLUSIONS: In conclusion, there is strong evidence that cisternal or ventricular lavage alone and in combination with kinetic therapy lead to a reduction of cerebral vasospasm and better outcome in patients suffering from subarachnoid hemorrhage. As a consequence a prospective randomized study would be of great interest.

Median aperture of the fourth ventricle revisited.

BACKGROUND: The median aperture of Magendie is the largest of three openings of the fourth ventricle and thus it forms the main path for the outflow of the cerebrospinal fluid from the ventricle. The Magendie aperture connects the fourth ventricle with the cisterna magna and makes a natural corridor for neurosurgical approach and inspection of the ventricle and its floor. The purpose of this study was to give a contemporary anatomical view of this structure in the context of historical data. MATERIAL AND METHODS: The Magendie foramen was studied in 30 fixed specimens of human brainstems with cerebella. The microdissection technique was used. Measurements were taken with a microscope ocular ruler. RESULTS: The aperture is limited by the following structures: obex and gracile tubercles inferiorly, and tela choroidea with choroid plexus superolaterally. Obex tubercles usually have the form of a piece of neural tissue bridging two halves of the brainstem above the entrance to the central canal. Gracile tubercles together are 8.15 mm wide and the maximal width of the foramen is 6.53 mm. Tela choroidea attaches laterally at both sides to the inferior medullary velum. In most cases the right and left choroid plexus are connected to each other with a triangular membrane of tela choroidea, which protrudes through the median foramen and attaches to the vermis at a highly variable level. CONCLUSIONS: We hope that the presented description of anatomical relations around the Magendie aperture, with its new measurements, will be helpful for those operating in the area and will explain some of the inaccuracies found in literature.

Comparison of high-dose intracisterna magna and lumbar puncture intrathecal delivery of AAV9 in mice to treat neuropathies.

Gene therapy clinical trials for neurological disorders are ongoing using intrathecal injection of adeno-associated virus (AAV) vector directly into the cerebral spinal fluid. Preliminary findings from these trials and results from extensive animal studies provides compelling data supporting the safety and benefit of intrathecal delivery of AAV vectors for inherited neurological disorders. Intrathecal delivery can be achieved by a lumbar puncture (LP) or intracisterna magna (ICM) injection, although ICM is not commonly used in clinical practice due to increased procedural risk. Few studies directly compared these delivery methods and there are limited reports on transduction of the PNS. To further test the utility of ICM or LP delivery for neuropathies, we performed a head to head comparison of AAV serotype 9 (AAV9) vectors expressing GFP injected into the cisterna magna or lumbar subarachnoid space in mice. We report that an intrathecal gene delivery of AAV9 in mice leads to stable transduction of neurons and glia in the brain and spinal cord and has a widespread distribution that includes components of the PNS. Vector expression was notably higher in select brain and PNS regions following ICM injection, while higher amounts of vector was found in the lower spinal cord and peripheral organs following LP injection. These findings support that intrathecal AAV9 delivery is a translationally relevant delivery method for inherited neuropathies.

Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension.

Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain is important for clearance of metabolic waste. Arterial pulsations are thought to drive flow, but this has never been quantitatively shown. We used particle tracking to quantify CSF flow velocities in PVSs of live mice. CSF flow is pulsatile and driven primarily by the cardiac cycle. The speed of the arterial wall matches that of the CSF, suggesting arterial wall motion is the principal driving mechanism, via a process known as perivascular pumping. Increasing blood pressure leaves the artery diameter unchanged but changes the pulsations of the arterial wall, increasing backflow and thereby reducing net flow in the PVS. Perfusion-fixation alters the normal flow direction and causes a 10-fold reduction in PVS size. We conclude that particle tracking velocimetry enables the study of CSF flow in unprecedented detail and that studying the PVS in vivo avoids fixation artifacts.

Teflon sponge shunt for recurrent arachnoid cyst.

A 50-year-old female presented with complaints of progressive ataxia. Investigations showed a large intradural arachnoid cyst located anterior to the brainstem. Following marsupialization of the cyst she improved remarkably in her symptoms. The symptoms recurred nine months later and investigations revealed recurrence of the cyst. The cyst was evacuated again and two Teflon sponge sheets were placed such that they traversed the length of the cyst cavity and extended into the cisterna magna. At follow-up after 25 months, there has been no recurrence of symptoms or the cyst. The role and advantages of Teflon sponge in such cases is evaluated.

Effect of graded hyperventilation on cerebral metabolism in a cisterna magna blood injection model of subarachnoid hemorrhage in rats.

In subarachnoid hemorrhage (SAH) with cerebrovascular instability, hyperventilation may induce a risk of inducing or aggravating cerebral ischemia. We measured cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRglc), and lactate (CMRlac) at different PaCO2 levels after experimental SAH in rats (injection of 0.07 mL of autologous blood into the cisterna magna). Four groups of Sprague-Dawley male rats were studied at predetermined PaCO2 levels: group A: normocapnia (5.01-5.66 kPa [38.0-42.0 mm Hg]); group B: slight hyperventilation (4.34-5.00 kPa [32.5-37.5 mm Hg]); group C: moderate hyperventilation (3.67-4.33 kPa [27.5-32.4 mm Hg]); group D: profound hyperventilation (3.00-3.66 kPa [22.5-27.4 mm Hg]). Each of the four groups included eight rats with SAH and eight sham-operated controls. CBF was determined by the intracarotid Xe method; CMRo2, CMRglc, and CMRlac were obtained by cerebral arteriovenous differences. In both SAH rats and controls, hyperventilation decreased CBF in proportion to the decrement in PaCO2 without affecting either CMRO2, CMRglc, or CMRlac. In groups C and D, CBF decreased by 20%-35%, but CMRs were maintained by a compensatory increase in oxygen extraction fraction (OEF). The results show that even profound hyperventilation in this model of SAH is associated with an adequate increase in OEF so that CMRs of oxygen, glucose, and lactate remain similar to levels observed in normocapnic conditions.

An applicable method of drawing cerebrospinal fluid in rats.

BACKGROUND: Component analysis of cerebrospinal fluid (CSF) is frequently required to probe the causes and pathologic mechanisms of disease and effective drugs in experimental studies of the central nervous system. Rat and mouse are two kinds of most frequently used animals in experimental studies. Rats are considered to be the most suitable animal for experimental analysis of CSF both on cost and manipulability as mice are too small for drawing CSF. However, drawing CSF from rats is still not easy, which makes many researchers choose bigger animals, such as rabbits. This paper introduced a highly applicable technique of CSF collection from cerebellomedullary cistern (CC) in rats. METHODS: CSF collection with this technique was performed by direct CC puncture using a collection apparatus with negative pressure. The apparatus consists of a 1ml syringe, a disposable intravenous infusion needle and a clip. The needle was cut and made less sharp than the original one to avoid injury to the brain and spinal cord. RESULTS: We have collected CSF multiple times from each rat with this approach and the collection lasted less than 30s each time on average. The length of the collection needles of the CSF was conformed to the different body sizes (weight) of the rats in the 3 groups. Compared with currently existing methods, this is faster, safer, simpler and repeatable. CONCLUSIONS: CSF collection by CC puncture using a negative pressure collection apparatus is fast to operate, safe to the rats, and maximum amount of CSF can be collected.

Visualization of Pulsatile CSF Motion Around Membrane-like Structures with both 4D Velocity Mapping and Time-SLIP Technique.

PURPOSE: We compared the depiction of pulsatile CSF motion obtained by 4-dimensional phase-contrast velocity mapping (4D-VM) with that by time-spatial labeling inversion pulse (time-SLIP) technique in the presence of membrane structures. MATERIALS AND METHODS: We compared the 2 techniques using a flow phantom comprising tubes with and without a thin rubber membrane and applied the techniques to 6 healthy volunteers and 2 patients to analyze CSF dynamics surrounding thin membrane structures, such as the Liliequist membrane (LM), or the wall of an arachnoid cyst. RESULTS: Phantom images exhibited propagation of the flow and pressure gradient beyond the membrane in the tube. In contrast, fluid labeled by the time-SLIP technique showed little displacement from the blockage of spin travelling by the membrane. A similar phenomenon was observed around the LM in healthy volunteers and the arachnoid cyst wall in a patient. CONCLUSION: Four-dimensional phase-contrast velocity mapping permitted visualization of the propagation of CSF pulsation through the intracranial membranous structures. This suggests that 4D-VM and the time-SLIP technique provide different information on flow and that both techniques are useful for classifying the pathophysiological status of CSF and elucidating the propagation pathway of CSF pulsation in the cranium.

Intracisternal antisense oligodeoxynucleotides to the thyrotropin-releasing hormone receptor blocked vagal-dependent stimulation of gastric emptying induced by acute cold in rats.

Cold exposure increases TRH gene expression in hypothalamic and raphe nuclei and results in a vagal activation of gastric function. We investigated the role of medullary TRH receptors in cold (4-6 C, 90 min)-induced stimulation of gastric motor function in fasted conscious rats using intracisternal injections of TRH receptor (TRHr) antisense oligodeoxynucleotides (100 microg twice, -48 and -24 h). The gastric emptying of a methyl-cellulose solution was assessed by the phenol red method. TRH (0.1 microg) or the somatostatin subtype 5-preferring analog, BIM-23052 (1 microg), injected intracisternally increased basal gastric emptying by 34% and 47%, respectively. TRHr antisense, which had no effect on basal emptying, blocked TRH action but did not influence that of BIM-23052. Cold exposure increased gastric emptying by 64%, and the response was inhibited by vagotomy, atropine (0.1 mg/kg, i.p.), and TRHr antisense (intracisternally). Saline or mismatched oligodeoxynucleotides, injected intracisternally under similar conditions, did not alter the enhanced gastric emptying induced by cold or intracisternal injection of TRH or BIM-23052. These results indicate that TRH receptor activation in the brain stem mediates acute cold-induced vagal cholinergic stimulation of gastric transit, and that medullary TRH may play a role in the autonomic visceral responses to acute cold.

Effect of centrally administered encephalinamides on regional cerebral blood flow in the dog.

(D-ala2)-met5-encephalinamide (AM encephalinamide) and (D-ala2)-leu5-encephalinamide (AL encephalinamide) were administered into the cisterna magna in anesthetized dogs to determine whether these opiates effected the neurohypophyseal circulation differently than the circulation of other brain areas. At the beginning of the experimental protocol, animals were given either mock cerebral spinal fluid (CSF) or 5 or 25 mg of AM encephalinamide or 5 mg of AL encephalinamide in equal volumes of mock CSF into the cisterna magna. By 60 min after intracisternal injection, radiolabeled AM encephalinamide distributed throughout the brain with the highest concentration being in the area of the brainstem. Sixty minutes after intracisternal injection, heart rate was decreased 29.0 +/- 5.1%, 41.3 +/- 4.4%, and 36.0 +/- 3.6%, and MABP was decreased 25.2 +/- 8.0%, 26.4 +/- 2.4%, and 32.3 +/- 2.6% in animals treated with AL encephalinamide (5 mg), AM encephalinamide (5 mg), and AM encephalinamide (25 mg), respectively. Neither AL encephalinamide or AM encephalinamide altered CBF or CMRO2 when compared with animals treated with mock CSF, whereas both AL encephalinamide and AM encephalinamide reduced neurohypophyseal blood flow by 30 min (43 +/- 11%, AL encephalinamide; 35 +/- 7%, AM encephalinamide, 5 mg; 46 +/- 8%, AM encephalinamide, 25 mg); the reduction was sustained throughout the 60-min protocol (34 +/- 10%, AL encephalinamide; 37 +/- 3%, AM encephalinamide, 5 mg; 38 +/- 4% AM encephalinamide, 25 mg). Plasma arginine vasopressin was transiently elevated 15 (326 +/- 75%, AL encephalinamide; 323 +/- 109%, AM encephalinamide, 25 mg) and 30 min (271 +/- 68%, AL encephalinamide; 368 +/- 136%, AM encephalinamide, 25 mg) in animals treated with AL encephalinamide or AM encephalinamide (25 mg). Intravenous naloxone administered at the end of the 60-min encephalinamide protocol was associated with a rise toward control values in heart rate and MABP in the AL encephalinamide group and in heart rate, MABP, and neurohypophyseal blood flow in both the AM encephalinamide 5 mg and 25 mg groups. These data suggest that encephalinamides may play a role in the regulation of neurohypophyseal blood flow through their actions on opiate receptors.

The identity of the unconditioned stimulus to the central nervous system is interferon-beta.

The specific mechanism of interaction between the central nervous system and immune system was examined using conditioned augmentation of natural killer (NK) cell activity. This study focused on the role of interferon-beta (IFN-beta) as the unconditioned stimulus (US). IFN-beta was found to be the signal responsible for the bidirectional communication which links the central nervous system with the immune system. This was substantiated by injection of small quantities of IFN-beta directly into the cisterna magna, which activated the effector pathway from the central nervous system to the immune system. More importantly, we found that when the conditioned stimulus (CS) was paired with an injection of IFN-beta into the cisterna magna, the conditioned animals were able to raise their natural killer cell activity in response to subsequent exposure to the conditioned stimulus. These studies show the unconditioned response must be the response of the central nervous system (CNS) to the unconditioned stimulus and not the direct effect of the substance injected into the periphery.

Studies of cerebrospinal fluid flow and penetration into brain following lateral ventricle and cisterna magna injections of the tracer [14C]inulin in rat.

Parasynaptic communication, also termed volume transmission, has been suggested as an important means to mediate information transfer within the central nervous system. The purpose of the present study was to visualize by autoradiography the available channels for fluid movement within the extracellular space following injection of the inert extracellular marker [14C]inulin into the lateral ventricle or cisterna magna. Bolus injections of 5 microl of 1 microCi of [14C]inulin were made in awake rats via chronically implanted cannulae. After survival times ranging from 5 min to 4 h, brains were processed for in vivo autoradiography. At 5 min the tracer distributed throughout the ventricles, subarachnoid spaces and cisterns "downstream" of the injection sites. Penetration into the brain from these sites was complex with preferential entry along the ventral side of the brain, especially into the hypothalamus and brainstem. By 4 h virtually the entire brain was labeled irrespective of the site of tracer application. Sustained tracer entry from subarachnoid spaces suggests that some areas act as depots to trap circulating material. This mechanism may contribute to the pattern of deep penetration at later time-points. The spatial and temporal characteristics of fluid movement throughout the brain are instructive in the interpretation of many experimental procedures involving injection of molecules into the cerebrospinal fluid.

Release of beta-endorphin immunoreactivity from brain by activation of a hypothalamic N-methyl-D-aspartate receptor.

Lateral ventricle-cisterna magna perfusion in the halothane-anesthetized rat was used as a model to study beta-endorphin release in the brain. Microinjection of N-methyl-D-aspartate into the arcuate nucleus of the hypothalamus released beta-endorphin immunoreactivity into perfusate and the release was blocked by systemic pretreatment with the N-methyl-D-aspartate antagonist dizocilpine (MK-801). N-methyl-D-aspartate microinjections did not increase beta-endorphin immunoreactivity in plasma, and pretreatment with dexamethasone did not prevent release of beta-endorphin immunoreactivity into perfusate, emphasizing that the released beta-endorphin immunoreactivity did not come from plasma. The non-N-methyl-D-aspartate glutamate receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide did not release beta-endorphin immunoreactivity. High-performance liquid chromatography characterization of perfusates collected after N-methyl-D-aspartate microinjection showed that a major part, but not all, of the beta-endorphin immunoreactivity co-eluted with authentic beta-endorphin. Microinjection of N-methyl-D-aspartate provoked an algogenic response in the anesthetized rat, and inhibited the motor and cardiovascular responses to tail immersion in 52.5 degrees C water. This block was reversed by pretreatment with MK-801, but not naloxone. Injection of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid hydrobromide elicited the same behavioral response and blocked the nociceptive tail-dip reaction, but did not release beta-endorphin immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin release from the ischaemic kidney.

1. We have confirmed that spinal section, and also pithing, inhibits the pressor response associated with the release of renin that follows re-establishment of circulation to the ischaemic rat kidney. Brain transections at bulbar and midthalamic levels did not modify the blood pressure elevation.2. Several pharmacological antagonists of the sympathetic nervous system did not modify the blood pressure response. These observations are not consistent with the view that a neural element is necessary for renin release.3. Constant flow perfusion of the ischaemic kidney in the intact and spinal sectioned rat was performed to evaluate haemodynamic factors involved in renin release. The pressor response was present in spinal sectioned animals under these conditions.4. These results suggest that the nervous system is necessary to maintain adequate blood flow for renin ;washout' into the systemic circulation rather than to release renin from juxtaglomerular cells.

Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: role of CRF(2).

1. Corticotropin-releasing factor (CRF) acts in the brain to inhibit thyrotropin-releasing hormone (TRH) analogue, RX-77368-induced vagal stimulation of gastric motility. We investigated CRF receptor-mediated actions of rat urocortin (rUcn) injected intracisternally (ic) on gastric motor function. 2. Urethane-anaesthetized rats with strain gauges on the gastric corpus were injected i.c. with rUcn and 20 min later, with i.c. RX-77368. CRF antagonists were injected i.c. 10 min before rUcn. 3. RX-77368 (1.5, 3, 10, 30 and 100 ng, i.c.) dose-dependently increased corpus contractions, expressed as total area under the curve (AUC, mV min(-1)) to 2.6+/-2.5, 6.1+/-5.9, 9.8+/-2.6, 69.7+/-21.7 and 74.9+/-28.7 respectively vs 0.2+/-0.1 after i.c. saline. Ucn (1, 3 or 10 microg) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.c. saline+RX-77368. 4. The CRF(1)/CRF(2) antagonist, astressin-B (60 microg, i.c.) completely blocked i.c. rUcn (3 microg, i.c.)-induced inhibition of gastric motility stimulated by RX-77368 (30 ng). 5. The selective CRF(2) antagonist, astressin(2)-B (30, 60 or 100 microg, i.c. ) dose-dependently prevented i.c. rUCn action while the CRF(1) antagonist, NBI-27914 did not. 6. In conscious rats, rUcn (0.6 or 1 microg, i.c.) inhibited gastric emptying of an ingested chow meal by 61 and 92% respectively. rUcn action was antagonized by astressin(2)-B. 7. These data show that i.c. rUcn acts through CRF(2) receptors to inhibit central vagal gastric contractile response and postoprandial emptying.

ICP monitoring in the rat: comparison of monitoring in the ventricle, brain parenchyma, and cisterna magna.

Various methods of continuous intracranial pressure (ICP) monitoring during experimental procedures in the rat have been described. However, no systematic comparison of ICP monitoring in the ventricle, brain parenchyma, and cisterna magna has been reported. Since accurate and reliable ICP measurements are important in experimental models of traumatic brain injury, the present study was conducted to compare simultaneous ICP measurements from ventricular, cisterna magna, and intraparenchymal monitors during ICP changes. Subdural hematoma was produced by infusion of 0.3 ml of autologous blood into the subdural space over 6 min. The ventricular and the intraparenchymal fiberoptic catheter produced reliable and comparable pressure recordings, that did not statistically differ (p = 0.4), throughout the one hour monitoring time. In contrast, the cisterna magna catheter was less reliable and produced significantly lower readings throughout the monitoring time (p<0.001). The intraparenchymal device produced greater cortical damage than the ventricular catheter. In conclusion, ventricular ICP monitoring is the preferred method under these circumstances, since it is accurate and induces least brain damage.

Behavioral effects of centrally administered arginine vasopressin in the rat fetus.

Arginine8 vasopressin (AVP) was administered to rat fetuses on Embryonic Day 20 via intracisternal (IC), intrahemispheric (IH), or intrathecal (IT) injection. The IC administration of AVP promoted a 4-fold increase in motor activity, including the uncommon patterns of mouthing, licking, and facial wiping. The IH injection of AVP had little effect on fetal behavior, but IT injection resulted in pronounced increases in fetal activity, including mouthing, licking, and wiping. The IT administration of a V1 antagonist blocked AVP effects, whereas IH injection potentiated AVP-induced changes in fetal behavior. The IC blockade of V1 receptors suppressed facial wiping to a chemosensory fluid (lemon) and reduced oral grasping of an artificial nipple, whereas IH injection of the V1 antagonist promoted facial wiping responses and increased grasping of the nipple. These data suggest that AVP may play a role in the development of responsiveness to stimuli encountered in the context of suckling.

Endogenous serotonin produces an inhibitory tone on vagally stimulated gastric function.

The effect of depletion of serotonin stores on vagally stimulated gastric acid secretion and motility was studied in rats. Pretreatment of rats with parachlorophenylalanine (p-CPA) produced a 57% reduction in the intraluminal gastric release of serotonin and a 43-100% potentiation of the gastric acid secretory response elicited by intracisternal injection of the stable TRH analogue RX 77368 in conscious pylorusligated rats or in urethane-anesthetized rats with an acute gastric fistula. p-CPA also enhanced the vagally stimulated gastric acid output produced by intravenous injection of baclofen. In contrast, p-CPA pretreament had no effect on gastric acid secretion stimulated by bethanechol, histamine, or pentagastrin. Selective depletion of central serotonin stores by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) given alone or combined with parachloroamphetamine pretreatment did not alter RX 77368-stimulated gastric acid secretion. In addition, gastric contractility stimulated by intracisternal injection of RX 77368 was significantly enhanced by p-CPA but not by 5,7-DHT pretreatment; whereas the contractile response to carbachol was not altered by p-CPA pretreatment. These results suggest that depletion of peripheral but not central serotonergic stores potentiates gastric acid secretion and contractility stimulated by vagally, but not peripherally, acting gastric stimulants. Thus, peripheral serotonin may exert an inhibitory tone on vagally stimulated gastric acid secretion and motility in the rat.

X-irradiation-induced loss of O-2A progenitor cells in rat spinal cord is inhibited by implants of cells engineered to secrete glial growth factor 2.

The loss of O-2A progenitor cells has been implicated as a critical event in radiation-induced spinal cord demyelination. To investigate whether glial growth factor 2 (GGF2) affects the number of O-2A cells in the irradiated rat cervical spinal cord, an ex vivo gene therapy approach was applied in which CHO cells engineered to express recombinant human GGF2 were injected into the cisterna magna of adult rats. Spinal cord irradiation reduced the number of O-2A cells in a dose-dependent manner. However, this radiation-induced decrease in O-2A progenitor cells was significantly attenuated by the delivery of GGF2 after irradiation. These data indicate that the cell-mediated delivery of GGF2 can reduce the loss of O-2A progenitors after irradiation.