Can early clinical parameters predict post-traumatic pituitary dysfunction in severe traumatic brain injury?

BACKGROUND: Post-traumatic hypopituitarism is a major complication after severe head trauma. The aim of our study was to evaluate the possible role of early clinical parameters in the development of endocrine deficits. METHODS: Data on endocrine function, on-admission clinical-, laboratory-, and ICU-monitored parameters were available in 63 patients of the surviving 86 severe head injury patients (post-resuscitation GCS under 8) treated at one neurosurgical center during a 10-year period. RESULTS: Hypopituitarism was diagnosed in 68.3 % of the patients. The most frequently affected pituitary axis was the growth hormone (GH): GH deficiency or insufficiency was present in 50.8 %. Central hypogonadism affected 23.8 % of male patients; hypothyroidism and secondary adrenal failure were found in 22.2 and 9.5 % of the investigated population, respectively. Early onset (within 1 year of brain injury) hypopituitarism was found in 24 patients. No connection was found between the development of hypopituitarism and any of the clinical parameters assessed on-admission or at ICU. Significant correlations were found between early endocrine dysfunctions and surgical intervention (OR: 4.64) and the diagnosis of subdural hematoma (OR: 12). In our population, after road traffic accidents, the development of late-onset hypopituitarism was less prevalent (OR: 0.22). CONCLUSIONS: Since our results do not indicate any reliable predictive parameter for the development of endocrine dysfunction in a cohort of patients with severe traumatic brain injury, regular endocrine screening of this specific patient population seems obligatory.

Lateralisation of non-metric rhythm.

There are contradictory results on lateralisation and localisation of rhythm processing. Our aim was to test whether there is a hemispheric dissociation of metric and non-metric rhythm processing. We created a non-metric rhythm stimulus without a sense of metre and we measured brain activities during passive rhythm perception. A total of 11 healthy, right-handed, native female Hungarian speakers aged 21.3 ± 1.1 were investigated by functional magnetic resonance imaging (fMRI) using a 3T MR scanner. The experimental acoustic stimulus consisted of comprehensive sentences transformed to Morse code, which represent a non-metric rhythm with irregular perceptual accent structure. Activations were found in the right hemisphere, in the posterior parts of the right-sided superior and middle temporal gyri and temporal pole as well as in the orbital part of the right inferior frontal gyrus. Additional activation appeared in the left-sided superior temporal region. Our study suggests that non-metric rhythm with irregular perceptual accents structure is confined to the right hemisphere. Furthermore, a right-lateralised fronto-temporal network extracts the continuously altering temporal structure of the non-metric rhythm.

Quantitative proton MRI and MRS of the rat brain with a 3T clinical MR scanner.

OBJECTIVE: To demonstrate the capability of a clinical 3T human scanner in performing quantitative MR experiments in the rat brain. MATERIAL AND METHODS: In vivo, measurements on eight Wistar rats were performed. Longitudinal relaxation time (T1) and transverse relaxation time (T2) measurements were set up at a spatial resolution of 0.3×0.3×1mm(3). Diffusion-weighted imaging was also applied and the evaluation included both mono- and biexponential approaches (b-value up to 6000s/mm(2)). Besides quantitative imaging, the rat brain was also scanned at a microscopic resolution of 130×130×130µm(3). Quantitative proton spectroscopy was also carried out on the rat brain with water as internal reference. RESULTS: T1 and T2 for the rat brain cortex were 1272±85ms and 75±2ms, respectively. Diffusion-weighted imaging yielded accurate diffusion coefficient measurements at both low and high b-value ranges. The concentrations of MR visible metabolites were determined for the major resonances (i.e., N-acetyl-aspartate, choline and creatine) with acceptable accuracy. CONCLUSION: The results suggest that quantitative imaging and spectroscopy can be carried out on small animals on high-field clinical scanners.

1H-MRS experiences after bilateral DBS of the STN in Parkinson's disease.

UNLABELLED: The objective of this study was to evaluate the changes in the concentrations of certain brain metabolites in 13 patients with Parkinson's disease before and after bilateral subthalamic nucleus (STN DBS). The N-acetylaspartate (NAA)/choline (Chol), NAA/creatine (Cr), Chol/Cr ratios were determined by single voxel Proton magnetic resonance spectroscopy ((1)H-MRS) studies on 1.0T unit using short TE stimulated echo acquisition mode (STEAM) sequence. Spectra were obtained from the right and left globus pallidus, and left fronto-basal cortex. The patients were also assessed according to the UPDRS part III, in the "medication-on and off" conditions. CONCLUSIONS: after STN DBS cortical NAA/Cho, NAA/Cr ratios increased significantly, which were highly correlated with the significant improvements of the UPDRS scores.

Rescuing neurons and glia: is inhibition of apoptosis useful?

Traumatic brain injury (TBI) represents a leading cause of death in western countries. Despite all research efforts we still lack any pharmacological agent that could effectively be utilized in the clinical treatment of TBI. Detailed unraveling of the pathobiological processes initiated by/operant in TBI is a prerequisite to the development of rational therapeutic interventions. In this review we provide a summary of those therapeutic interventions purported to inhibit the cell death (CD) cascades ignited in TBI. On noxious stimuli three major forms of CD, apoptosis, autophagia and necrosis may occur. Apoptosis can be induced either via the mitochondrial (intrinsic) or the receptor mediated (extrinsic) pathway; endoplasmic reticular stress is the third trigger of caspase-mediated apoptotic processes. Although, theoretically pan-caspase inhibition could be an efficient tool to limit apoptosis and thereby the extent of TBI, potential cross-talk between various avenues of CD suggests that more upstream events, particularly the preservation of the cellular energy homeostasis (cyclosporine-A, poly ADP ribose polymerase (PARP) inhibition, hypothermia treatment) may represent more efficient therapeutic targets hopefully also translated to the clinical care of the severely head injured.

Ablative stereotactic surgery improves manual performance time in Parkinson's disease.

The objective of this study was to determine the influence of stereotactic ablative surgical interventions on the time required for the performance of manual tasks (i.e. performance time) in patients with Parkinson's disease (PD). We studied 28 patients after pallidotomy and pallido-thalamotomy who were evaluated at four time: before the operation, and 2 days, 3 and 6 months postoperatively. The speed of performance of handwriting and drawing were assessed by means of a chronometer using certain parts of an international standard scale (modified by Fahn). The patients were also assessed according to the Unified Parkinson's Disease Rating Scale (UPDRS) part III. The patients were divided into two groups. Those in group A had relief of all main Parkinsonian symptoms after pallidotomy including tremor. The patients in group B had no relief of tremor straight after pallidotomy. For them the pallidotomy was completed with thalamotomy in the same sitting, which had resulted in cessation of tremor. The time of performance of the manual tasks diminished significantly in all cases in both groups (Student's t-test: p<0.0001). No complications developed following pallidotomy. Pallido-thalamotomy caused transient adverse effects in two patients, and one patient developed permanent adverse effects such as dysarthria and dysequilibrium. Significant improvements were observed in the speed of handwriting and drawing in both groups, but pallido-thalamotomy was accompanied with complications.

[Microeletrode guided stereotactic pallidotomy and pallido-thalamotomy for treatment of Parkinson's disease]. / Tratamiento de la enfermedad de Parkinson con palidotomía y palido-talamotomíaestereotáctica guiada por microelectrodos.

OBJECTIVE: Authors evaluated the therapeutic effect of the MRI and microelectrodeguided stereotactic pallido- and pallido-thalamotomy in 33 patients with Parkinson's disease (PD), whose symptoms were refractory to pharmacological therapy. MATERIAL AND METHODS: The patients were evaluated according to the internationally standardized rating scales (UPDRS part II, III, Schawb & England, Hoehn & Yahr, and Fahn) at six timepoints: before the operation, and 2 days, 3, 6, 9 and 12 months postoperatively. The patients were divided into 2 groups. Those in group A had relief of all main parkinsonian symptoms after pallidotomy including tremor. The patients in group B had no relief of tremor after pallidotomy. For them the pallidotomy was completed by thalamotomy in the same sitting, which had resulted in cessation of tremor. RESULTS: The following results were obtained by using the UPDRS part III: after pallidotomy "On state" mean: preoperative 51.2, postoperative at 2nd day 29.5 at 3, 6 and 9th month 26, and at 12th month 28.7. "Off state" mean: preoperative 64.3, postoperative at 2nd day 31.6, at 3, 6 and 9th month 26, and at 12th months 30.5. After pallidothalamotomy "On state" mean: preoperative 43.5, postoperative at 2nd day 27.9, at 3rd month 22.9, at 6th month 22.8, and at 9 and 12th month 24.5. "Off state" mean: preoperative 62.6, postoperative at 2nd day 38, at 3rd month 30, at 6th month 31,8 and at 9 and 12th month 33.8. CONCLUSIONS: For those patients, whose tremor was not successfully controlled by pallidotomy, the combined pallido-thalamotomy was effective. The clinical symptomps, according to the rating scales, improved significantly in both groups (student t: P<0.0001), but bilateral lesioning carried higher surgical morbidity.

Cocaine- and amphetamine-regulated transcript peptide (CART) is a selective marker of rat granule cells and of human mossy cells in the hippocampal dentate gyrus.

Cocaine- and amphetamine-regulated transcript (CART) peptide immunocytochemistry was used to reveal cellular localization in the dentate gyrus and in Ammon's horn of the rat and human hippocampal formations. In the rat dentate gyrus, only granule cells were labeled, whereas in humans, only mossy cells of the hilar region expressed CART peptide immunoreactivity. In the rat, CART-positive granule cells were located at the molecular layer border of the granule cell layer and had no features that would distinguish them from other granule cells. The mossy fiber bundle was labeled in the hilus as well as along the entire CA3 area of Ammon's horn. In the human, CART-immunoreactive mossy cells displayed the characteristic thorny excrescences both on their somata and their main dendrites. Axon collaterals of mossy cells could be seen in the hilus and the main axons formed a dense band in the inner molecular layer of the dentate gyrus, suggesting that mossy cells are the principal source of the associational pathway. Granule cells of the dentate gyrus and pyramidal neurons of the human hippocampal formation were devoid of CART peptide immunoreactivity. A few labeled non-pyramidal cells and a large group of strongly immunostained axons of unknown origin were present in all layers of CA1-3. Granule cells are the main excitatory cell population of the dentate gyrus while mossy cells are in a key position in controlling activity of granule cells. The specific location of CART peptide in the dentate granule cells of rodents and in the mossy cells of the human hippocampus may indicate involvement of neuronal circuitry of the dentate gyrus in the memory-related effects of cocaine and amphetamine. Independently of its functional role, CART peptide can be used as a specific marker of human mossy cells and of the dentate associational pathway. The sensitivity of CART peptide to postmortem autolysis may restrict the use of this marker in surgically removed hippocampi or in human brains removed and fixed shortly after death.

Studies of mdx mice.

Cerebral water accumulation-clinically denoted as brain edema-is a potentially life threatening complication of almost every intracranial neuropathological state. The molecular membrane water channel aquaporin-4 (AQP4) has been shown to be present at the blood-brain barrier (BBB) where it plays pivotal role in the transport of water between the tissue water compartments of the brain. Accumulating evidence indicates that the blockade of AQP4 function at the BBB would be a new therapeutic approach to the treatment and prevention of brain swelling. The cytoskeletal protein dystrophin has been shown to be involved in the maintenance of the polarized expression of AQP4 at the BBB. In order to further elucidate the mechanisms responsible for the highly polarized AQP4 expression, we studied brain tissue water accumulation during induction of brain edema in dystrophin-null transgenic mice (mdx-bgeo) and control mice. Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null brains revealed a dramatic reduction of AQP4 in astroglial end-feet surrounding capillaries (BBB) and at the glia limitans (cerebrospinal fluid-brain interface). The AQP4 protein is mislocalized, because immunoblotting showed that the total AQP4 protein abundance was unaltered. Brain edema was induced by i.p. injection of distilled water and 8-deamino-arginine vasopressin. Changes in cerebral water compartments were assessed by diffusion-weighted MRI (DWI) with determination of the apparent diffusion coefficient (ADC). In dystrophin-null mice and control mice, ADC gradually decreased by 5-6% from baseline levels during the first 35 min, indicating the initial phase of intracellular water accumulation is similar in the two groups. At this point, the control mice sustained an abrupt, rapid decline in ADC to 58%+/-2.2% of the baseline at 52.5 min, and all of the animals were dead by 56 min. After a consistent delay, the dystrophin-null mice sustained a similar decline in ADC to 55%+/-3.4% at 66.5 min, when all of the mice were dead. These results demonstrate that dystrophin is necessary for polarized distribution of AQP4 protein in brain where facilitated movements of water occur across the BBB and cerebrospinal fluid-brain interface. Moreover, these results predict that interference with the subcellular localization of AQP4 may have therapeutic potential for delaying the onset of impending brain edema.

Preinjury administration of the calpain inhibitor MDL-28170 attenuates traumatically induced axonal injury.

Traumatic brain injury (TBI) evokes diffuse (traumatic) axonal injury (TAI), which contributes to morbidity and mortality. Damaged axons display progressive alterations gradually evolving to axonal disconnection. In severe TAI, the tensile forces of injury lead to a focal influx of Ca2+, initiating a series of proteolytic processes wherein the cysteine proteases, calpain and caspase modify the axonal cytoskeleton, causing irreversible damage over time postinjury. Although several studies have demonstrated that the systemic administration of calpain inhibitors reduces the extent of ischemic and traumatic contusional injury a direct beneficial effect on TAI has not been established to date. The current study was initiated to address this issue in an impact acceleration rat-TBI model in order to provide further evidence on the contribution of calpain-mediated proteolytic processes in the pathogenesis of TAI, while further supporting the utility of calpain-inhibitors. A single tail vein bolus injection of 30 mg/kg MDL-28170 was administered to Wistar rats 30 min preinjury. After injury the rats were allowed to survive 120 min when they were perfused with aldehydes. Brains were processed for immunohistochemical localization of damaged axonal profiles displaying either amyloid precursor protein (APP)- or RMO-14-immunoreactivity (IR), both considered markers of specific features of TAI. Digital data acquisition and statistical analysis demonstrated that preinjury administration of MDL-28170 significantly reduced the mean number of damaged RMO-14- as well as APP-IR axonal profiles in the brainstem fiber tracts analyzed. These results further underscore the role of calpain-mediated proteolytic processes in the pathogenesis of DAI and support the potential use of cell permeable calpain-inhibitors as a rational therapeutic approach in TBI.

Biportal endoscopic management of third ventricle tumors in patients with occlusive hydrocephalus: technical note.

OBJECTIVE: To present the feasibility and advantages of the biportal endoscopic management of posterior third ventricle tumors. As a result of recent developments in neuroendoscopy, classical third ventriculostomy has become a standard single burr hole procedure and a real alternative to shunting in the treatment of occlusive hydrocephalus. In patients with third ventricle tumors occluding the aqueduct, the acute development of hydrocephalus may often precede debilitating focal symptoms and signs. Forty percent of those tumors are radiosensitive, rendering craniotomy unnecessary. The goal of primary management is the alleviation of raised intracranial pressure and determination of the histological nature of the tumor. Cerebrospinal fluid shunting and the performance of a computed tomography- or magnetic resonance imaging-guided biopsy are generally suggested as the methods of choice. METHODS: Three patients with posterior third ventricle tumors and acute hydrocephalus were treated in one session by computed tomography-guided endoscopic third ventriculostomy and endoscopic tumor biopsy was performed by means of two rigid ventriculoscopes. RESULTS: Ventriculostomy was performed in three patients, and tumor biopsy was performed in two patients. The maximum 40-minute operation did not involve mortality or morbidity. Histological findings were established in all patients. In two patients with malignant infiltrative tumors, postoperative radiotherapy was used; in one patient with a small cavernoma, no further measures were taken. At the 6-month follow-up, flow-sensitive magnetic resonance imaging confirmed ventriculostomy patency in all patients. CONCLUSION: The biportal endoscopic approach allowed independent visual control of both procedures, safe passages of the ventriculoscopes via the narrow foramen of Monro, and facile control of the intracranial pressure in the ventricles via the available four irrigation channels during the performance of tumor biopsy and fenestration of the floor of the third ventricle. In selected patients with infiltrating posterior third ventricle tumors, this procedure and postoperative radiotherapy may be an alternative to direct surgery or to shunting and performance of image-guided biopsy.

The effect of skull and dura on brain volume regulation after hypo- and hyperosmolar fluid treatment.

This study was performed to determine the response of brain water and electrolytes to acute hypo-osmolality and hyperosmolality in animals with intact skulls and dura, in comparison with those subjected to extensive bilateral or unilateral craniectomy and opening of the dura. In rats, 4 to 5 weeks after extensive unilateral or bilateral craniectomy and opening of the dura, a 50-mOsm/kg decrease in plasma osmolality was produced by systemic administration of distilled water ("water intoxication"), or a 28-mOsm/kg increase in plasma osmolality was produced by systemic administration of either 1 M NaCl or 1 M mannitol in 0.34 M NaCl. Tissue water, Na. and K contents were determined after 120 minutes. Tissue water accumulation or water loss was proportional to the decrease or increase in plasma osmolality. The tissue water accumulation after "water intoxication," however, was less (40% of the predicted value) than that predicted for ideal osmotic behavior. The brain tissue was also found to shrink less than predicted on the basis of ideal osmotic behavior (40% of the predicted value after mannitol treatment, and 60% after NaCl administration). This nonideal osmotic response of the brain tissue is consistent with the finding in other studies and indicated a significant degree of volume regulation. Water and electrolyte changes did not differ between animals operated on and those not operated on, a fact which demonstrates that there are no effects of extensive skull and dura defects on tissue volume regulation under hypo- and hyperosmolar conditions encountered under clinical circumstances.(ABSTRACT TRUNCATED AT 250 WORDS)

5-hydroxytryptamine injected intraventricularly fails to influence the brain water content.

Measurement of the content of brain water and electrolytes after the intraventricular administration of 5-hydroxytryptamine in rats, with and without exposure to osmotic stress, failed to show water accumulation in the brain parenchyma. It is suggested that elevation of serotonin in the cerebrospinal fluid--resembling pathological situations such as subarachnoid hemorrhage--does not play a primary role in brain edema formation.

Syndrome of inappropriate secretion of antidiuretic hormone after subarachnoid hemorrhage.

The authors report a review of 290 patients admitted for the treatment of subarachnoid hemorrhage. Twenty-seven (9.3%) patients developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The diagnosis was established by means of daily laboratory investigations (serum electrolytes and osmolality; urine sodium and osmolality; and fluid balance). The patients were divided into two groups (severe and mild SIADH) on the basis of clinical symptoms and signs and laboratory findings. High values of urine osmolality and sodium concentration in patients with low values of serum osmolality and sodium concentration were demonstrated. Thirteen (4.5%) patients had severe and 14 (4.8%) patients had mild SIADH. The source of bleeding was not discovered in 14 patients (4.8%). Nearly 10% of the patients with an aneurysm on the anterior communicating artery developed SIADH. Fluid therapy for these patients is described, and the treatment of SIADH is discussed.

Disturbances of cerebrospinal fluid circulation during the acute stage of subarachnoid hemorrhage.

Radioisotope cisternography was performed and the erythrocyte and hemoglobin contents of the cerebrospinal fluid (CSF) were determined within the first 4 days after subarachnoid hemorrhage in 42 patients. The clinical condition of the patients was related to the severity of the CSF circulation disturbances. Thirty-five patients had some degree of disturbance of CSF flow, and only 2 of the 42 patients had normal flow. In 5 cases the cisternograms were inconclusive. The severity of CSF circulation disturbances correlated well with clinical condition. No relationship was found between the number of erythrocytes in the CSF and the development of CSF circulation disturbances. The CSF erythrocyte content did not correlate with the clinical condition. It is suggested that flow disturbances of the CSF during the acute stage of subarachnoid hemorrhage might play an important role in the pathomechanism of the disease.

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after head injury.

The authors report a review of 1808 patients admitted for the treatment of craniocerebral injuries. Eighty-four (4.6%) developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Two types of SIADH (severe and mild) were defined on the basis of laboratory findings and clinical signs. SIADH occurred in 0.6% of the patients with mild head injury, 10.6% of those with moderate head injury, and 4.7% of the patients with severe head injury. Regular measurements of serum electrolytes, osmolality, and urinary sodium depletion should be made during the treatment of patients suffering from head trauma because unexpected clinical deterioration may often have a reversible cause: SIADH.

Brain water accumulation after the central administration of vasopressin.

The intraventricular administration of vasopressin or DDAVP (desmopressin acetate) increased the brain water content from 78.2% to 79.2-79.5%. This was achieved without an accompanying water load. The applied water load alone did not increase the water content of the brain. There was no significant difference in the water content of the brain between animals treated with intraventricular vasopressin and intravenous water load and animals receiving only intraventricular vasopressin. The water content of the olfactory bulbs of the control animals was 3.8% higher than that of the hemispheres. While the water content of the hemispheres increased by 1.3%, that of the olfactory bulbs did so by 1.7% subsequent to the intraventricular administration of DDAVP. Measurement of the brain electrolyte content was not conclusive as to the mechanism of water permeability changes. The possible mechanism is discussed. Although no tissue or cerebrospinal fluid concentrations of vasopressin enabling comparison with clinical pathological conditions have been measured, it is suggested that increased secretion of vasopressin into the cerebrospinal fluid in conditions such as subarachnoid hemorrhage or intracranial hypertension of various origins might play a role in edema formation.

Increased concentration of atrial natriuretic factor in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage and raised intracranial pressure.

Plasma and cerebrospinal fluid (CSF) atrial natriuretic factors/peptides (ANFs/ANPs) were measured in 26 patients with normal or raised intracranial pressure (ICP) by means of an instant radioreceptor assay. All 26 patients were suffering from aneurysmal subarachnoid hemorrhage (SAH), and 11 had also developed raised ICP (ICP greater than 20 mm Hg). In SAH patients with normal ICP, the plasma levels of ANF were 20 to 200 pg/ml (mean +/- SE, 89 +/- 68 pg/ml); in the 11 SAH patients with raised ICP, however, ANF levels were 14 to 262 pg/ml (mean 114 +/- 79 pg/ml). The difference was not statistically significant. The ANF/ANP plasma levels in 6 healthy volunteers were 15 to 167 pg/ml (mean 77 +/- 32 pg/ml). Although the ANF/ANP concentration in the CSF of patients with normal ICP did not reach the lower limit of detectability (i.e., 4 pg/ml) in any case, in those with elevated ICP it was 14 to 120 pg/ml (mean 49 +/- 37 pg/ml). This difference was statistically highly significant. The results of this preliminary study suggest that the ANF/ANP concentration in human CSF is 1 to 2 orders lower than that in the plasma and that there is no significant correlation between ANF/ANP levels in the CSF and the plasma. After SAH in patients with raised ICP, there was an accompanying increase in the ANF/ANP concentration in the CSF, but the ANF/ANP concentration in the plasma was not changed significantly. Accordingly, a central ANF/ANP release might be hypothesized to play a causative or adaptive role in the neuroendocrine regulation of ICP dynamics, although this may simply be an epiphenomenon.

Regulation of brain water and electrolyte contents: the possible involvement of central atrial natriuretic factor.

The intraventricular administration of 0.2 or 2 micrograms of synthetic rat atrial natriuretic factor (syn rANF), sequence 101-126 of the precursor, prevented the water accumulation elicited in rat brain by a systemic hypoosmolar fluid load and led to a statistically significant sodium loss from the nervous tissue, while the potassium content remained unaltered. Similar syn rANF administration to rats not treated with a hypoosmolar fluid load caused no significant change in the water, potassium, and sodium content of the hemispheres. In this experiment, a primary systemic action of centrally administered syn rANF with ensuing secondary changes in brain ion and water homeostasis seems unlikely, as the serum osmolality and sodium and potassium concentrations remained unaltered. Thus, a central influence of the intraventricularly administered hormone upon the water and ion balances of the nervous tissue can be hypothesized. The significant loss of sodium may reflect the primary role of volume regulation of the nervous tissue, i.e., the loss of extracellular osmols such as Na+ in response to a hypoosmolar environment. These data lend further support to the concept that a central neuroendocrine system regulates brain ion and volume homeostasis. The possible role of ANF in the management of brain edema should be considered.

Effects of intraventricularly injected isoosmolar glycerol on brain water and electrolytes in the rat.

The infusion of isoosmolar glycerol (0.35 mol/dm-3) into the ventricles of laboratory rats for 120 minutes led to an increase in the serum osmolality by 11 mosm/kg and to hypernatremia. The brain water content of the cerebral hemispheres decreased by 0.9% (P less than 0.05). A corresponding intraventricular infusion of saline or d-glucose did not cause significant changes in these parameters. These findings support the view that glycerol, even in a dose incapable of creating a major osmotic gradient between plasma and brain, could have a beneficial effect in the control of intracranial volume-pressure perturbations. It is hypothesized that, besides acting as an osmotic dehydrating agent in certain concentrations, glycerol influences the central neuroendocrine system responsible for brain ion and volume homeostasis. By its presumed reduction of central and peripheral vasopressin release through lowering the cerebrospinal fluid sodium concentration, it may help in decreasing the brain water content.