Development of an experimental model of neurocysticercosis-induced hydrocephalus. Pilot study

ABSTRACT PURPOSE: To develop an experimental model of neurocysticercosis-induced hydrocephalus METHODS: There were used 17 rats. Ten animals were inoculated with Taenia crassiceps cysts into the subarachnoid. Five animals were injected with 0.1ml of 25% kaolin (a standard solution for the development of experimental hydrocephalus) and two animals were injected with saline. Magnetic resonance imaging (MRI) was used to evaluate enlargement of the ventricles after one or three months of inoculation. Volumetric study was used to quantify the ventricle enlargement. RESULTS: Seven of the 10 animals in the cyst group developed hydrocephalus, two of them within one month and five within three months after inoculation. Three of the five animals in the kaolin group had hydrocephalus and none in the saline group. Ventricle volumes were significantly higher in the 3-months MRI cyst subgroup than in the 1-month cyst subgroup. Differences between cyst subgroups and kaolin group did not reach statistical significance. CONCLUSION: The developed model may reproduce the human condition of neurocysticercosis-related hydrocephalus, which exhibits a slowly progressive chronic course.

Central injection of captopril inhibits the blood pressure response to intracerebroventricular choline

In the present study, we investigated the involvement of the brain renin-angiotensin system in the effects of central cholinergic stimulation on blood pressure in conscious, freely moving normotensive rats. In the first step, we determined the effects of intracerebroventricular (icv) choline (50, 100 and 150 µg) on blood pressure. Choline increased blood pressure in a dose-dependent manner. In order to investigate the effects of brain renin-angiotensin system blockade on blood pressure increase induced by choline (150 µg, icv), an angiotensin-converting enzyme inhibitor, captopril (25 and 50 µg, icv), was administered 3 min before choline. Twenty-five µg captopril did not block the pressor effect of choline, while 50 µg captopril blocked it significantly. Our results suggest that the central renin-angiotensin system may participate in the increase in blood pressure induced by icv choline in normotensive rats.

Opiatergic participation in the thirst-inhibiting effect of acute third ventricle injections of cadmium (Cd 2+ ) and lead (Pb 2+ )

We have previously demonstrated that acute third ventricle injections of both lead and cadmium prevent the dipsogenic response elicited by dehydration or by central injections of dipsogenic agents such as angiotensin II, carbachol and isoproterenol in rats. We have also shown that the antidipsogenic action of cadmium may be due, at least in part, to activation of thirst-inhibitory central serotonergic pathways. In the present paper we show that in Wistar male rats the antidipsogenic effect of both lead acetate (3.0 nmol/rat) and cadmium chloride (3.0 nmol/rat) may be partially dependent on the activation of brain opiatergic pathways since central injections of naloxone (82.5 nmol/rat), a non-selective opioid antagonist, blunt the thirst-inhibiting effect of these metals. One hundred and twenty minutes after the second third ventricle injections, dehydrated animals (14 h overnight) receiving saline + sodium acetate displayed a high water intake (7.90 ñ 0.47 ml/100 g body weight) whereas animals receiving saline + lead acetate drank 3.24 ñ 0.47 ml/100 g body weight. Animals receiving naloxone + lead acetate drank 6.94 ñ 0.60 ml/100 g body weight. Animals receiving saline + saline drank 8.16 ñ 0.66 ml/100 g body weight whilst animals receiving saline + cadmium chloride drank 1.63 ñ 0.37 ml/100 g body weight. Animals receiving naloxone + cadmium chloride drank 8.01 ñ 0.94 ml/100 g body weight. It is suggested that acute third ventricle injections of both lead and cadmium exert their antidipsogenic effect by activating thirst-inhibiting opioid pathways in the brain

Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of cabachol

We investigated the effects of losartan, an AT1-receptor blocker, and ramipril, a converting enzyme inhibitor, on the pressor response induced by angiotensin II (ANG II) and carbachol (a cholinergic receptor agonist). Male Holtzman rats (250-300 g) with a stainless steel cannula implanted into the lateral ventricle (LV) were used. The injection of losartan (50 nmol/l mul) into the LV blocked the pressor response induced by ANG II (12 ng/1 mul) and carbachol (2 nmol/ 1 mul). After injection of ANG II and carbachol into the LV, mean arterial pressure (MAP) increased to 31 + 1 and 28 + 2 mmHg, respectively. Previous injection of losartan abolished the increase in MAP induced by ANG II and carbachol into the LV (2 + 1 and 5 + 2 mmHg, respectively). The injection of ramipril (12 ng/ 1 mul) prior to carbachol blocked the pressor effect of carbachol to 7 + 3 mmHg. These results suggests an interaction between central cholinergic pathways and the angiotensinergic system in the regulation of arterial blood pressure.

Lead (Pb+) and cadmium (Cd2+) inhibit the dipsogenic action of central beta-adrenergic stimulation by isoproterenol

We have previously demonstrated that acute third ventricle injections of both Pb2+ and Cd2+ impair the dipsogenic response elicited by three different situations: dehydration and central cholinergic or angiotensinergic stimulation. beta-Adrenergic activation is part of the multifactorial integrated systems operating in drinking behavior control in the central nervous system. In the present study acute third ventricle injections of Pb2+ (3,30 and 300 pmol/rat) or Cd2+ (0.3, 3 and 30 pmol/rat) blocked the dipsogenic response induced by third ventricle injections of isoproterenol (ISO; 160 nmol/rat) in a dose-dependent manner. Normohydrated animals receiving ISO + NaAc (sodium acetate) or saline (controls) displayed a high water intake after 120 min (ISO + saline = 5.78 ñ O.54 ml/lOO g; ISO + NaAc = 6.00 ñ O.6 ml/lOO g). After the same period,animals receiving ISO but pretreated with PbAc at the highest dose employed (300 pmol/rat) drank O.78 ñ O.23 ml/lOO g while those receiving ISO and pretreated with the highest dose of CdCl(2)(30 pmol/rat) presented a water intake of O.7 ñ O.30 ml/lOO g. Third ventricle injections of CdCl(2) (3 nmol/rat) or PbAc (3 nmol/rat) did not modify food intake in rats deprived of food for 24 h. Thus, general central nervous system depression explaining the antidipsogenic action of the metals can be safely excluded. It is concluded that both Pb2+ and Cd2+ inhibit water intake induced by central beta-adrenergic stimulation.

Effect of intracerebroventricular injection of ramipril on the drinking response caused by injection of noradrenaline into the third ventricle

We studied the effect of ramipril injected into the third ventricle (3rdV) on the control of water intake induced by injection of noradrenaline into the 3rdV of adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel cannula into the 3rdV. The injection volume was always 1mul and was injected over a period of 30-60 sec. Control animals were injected with 0.15 M NaCl. After the injection of isotonic saline (control, O.15 M NaCl) into the 3rdV, water ingestion was 0.3 ñ 0.1 ml/h. Ramipril(l mug/mul)injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 ñ 0.2 ml/h). The injection of noradrenaline (40 nmol/mul) after isotonic saline induced an increase in water intake (3.0 ñ 1.1 ml/h). The prior injection of ramipril decreased this ingestion to 1.8 + 0.3 ml/ h. These data show that the inhibition of converting enzyme in the brain reduces the water intake induced by catecholaminergic stimulation. We conclude that the brain is able to transform the prodrug ramipril into the active drug ramiprilat.

Central hyperthermic effect of arsenic in rabbits.

Hyperthermic effect of arsenic was investigated in rabbits. Injections of arsenic trioxide (0.0001 to 0.1 micrograms) into a lateral cerebral ventricle of the rabbit evoked a dose-dependent hyperthermia, respiratory stimulation and peripheral vasodilatation. Heat loss through respiratory stimulation and peripheral vasodilatation appeared responsible for the long latent period and the slight hypothermia sometimes obtained during this period as these effects followed the same time course. These effects were centrally mediated as demonstrated by the lack of efficacy of the same doses by the intravenous route. The hyperthermic effect of arsenic was antagonized by the sulphydryl donator, dimercaprol, the a-adrenoceptor blocking agent-phenoxybenzamine and the PG-synthesis inhibitor-aspirin. Multiple sites, for antagonistic effects of these substances can be explained by the action of arsenic in inactivating sulphydryl containing enzymes which are many and catalyze diverse biochemical reactions.

Effect of centrally administered glucagon on urinary sodium and potassium concentration in dogs.

The effects of glucagon administration through intracerebroventricular (ICV), third ventricular (TV) and intracisternal (I") routes on urinary sodium and potassium concentration have been studied in mongrel dogs. The central administration of glucagon resulted in a significant decrease in urinary sodium concentration (P less than 0.01) and increase in urinary potassium concentration (P less than 0.001). This change in urinary sodium and potassium concentration on central administration of glucagon was abolished in animals which were ventured to either sympathetic denervation or adrenalectomy. The observations in the present study suggest that the changes in urinary sodium and potassium concentration on central administration of glucagon, are due to increased secretion of some substance from the adrenals and the probable efferents might be the sympathetic fibres.

Central component of the cario-accelerator action of angiotensin II in dogs.

Injection of angiotensin II into a lateral cerebral ventricle (I.C.V.) or into a peripheral vein of anaesthetized dog elicited a rise in blood pressure and transient bradycardia followed by sustained tachycardia. Spinal transection at C2 and bilateral vagotomy abolished the central cardiovascular effect of I.C.V. angiotensin. However, in spinal transected dogs the usual pressor response to intravenous angiotensin was observed. Since the transient bradycardia was absent in bilaterally vagotomized dogs or in dogs with their blood pressure stabilized by means of a mechanical buffer devise it must be reflex in origin. The tachycardia was more marked in vagotomized dogs. Prior administration of a beta adrenergic receptor blocking agent propranolol, blocked the tachycardia, but the pressor response was unaffected. The cardiovascular responses to centrally administered angiotensin were practically abolished by prior treatment of dogs with reserpine or by extirpation of both adrenal glands. Thus it may be concluded that ICV angiotensin induces a centrogenic release of catecholamines from the adrenal medulla which is responsible for the cardiovascular responses.