Intraparenchymal Vessels Research Articles

Focal laminar cortical infarcts following aneurysmal subarachnoid haemorrhage

The aim of this prospective study was to analyse small band-like cortical infarcts after subarachnoid haemorrhage (SAH) using magnetic resonance imaging (MRI) with reference to additional digital subtraction angiography (DSA). In a 5-year period between January 2002 and January 2007 10 out of 188 patients with aneurysmal SAH were evaluated (one patient Hunt and Hess grade I, one patient grade II, four patients grade III, two patients grade IV, and two patients grade V). The imaging protocol included serially performed MRI with diffusion- and perfusion-weighted images (DWI/PWI) at three time points after aneurysm treatment, and cerebral vasospasm (CVS) was analysed on follow-up DSA on day 7+/-3 after SAH. The lesions were located in the frontal lobe (n=10), in the insular cortex (n=3) and in the parietal lobe (n=1). The band-like infarcts occurred after a mean time interval of 5.8 days (range 3-10 days) and showed unexceptional adjacent thick sulcal clots. Seven out of ten patients with cortical infarcts had no or mild CVS, and in the remaining three patients DSA disclosed moderate (n=2) or severe (n=1) CVS. The infarct pattern after aneurysmal SAH includes cortical band-like lesions. In contrast to territorial infarcts or lacunar infarcts in the white matter which develop as a result of moderate or severe proximal and/or distal vasospasm visible on angiography, the cortical band-like lesions adjacent to sulcal clots may also develop without evidence of macroscopic vasospasm, implying a vasospastic reaction of the most distal superficial and intraparenchymal vessels.

Intramicrovascular behavior of platelets in rat brain observed by high-speed laser confocal fluorescence microscopy

Although abundant data are available on in vitro platelet behavior, in situ studies in the brain microvasculature, especially in the intraparenchymal vessels, have not previously been possible because of methodological difficulties. We used our newly developed high-speed (125-1000 frames per sec) confocal fluorescence microscopy and image analysis system employing Matlab and our own KEIO-IS1 and KEIO-IS2 software to visualize platelet flow, tracking individual platelets in the microvasculature in living rat cerebral cortex. The program exploits the light intensity difference between the dark background and the light platelets in the visual field of the microscope to detect the platelets automatically. A small cranial window was trephined in the parietal region of urethane-anesthetized Wistar rats (n=10). Fluorescein isothiocyanate (FITC)-dextran (70 kDa) was injected intravenously to stain the microvessels. Subsequently, carboxylfluorescein succinimidyl ester (CFSE) was also injected intravenously to label platelets. Platelets in circulating blood became visible as bright particles in the intraparenchymal microvessels. In the veins, platelets were seen flowing slowly along endothelial cell walls (rolling) with a standard video camera at 30 frames per sec for a couple of minutes after the CSFE injection. In the arteries/arterioles, flowing platelets were detected only at high speed settings (125-1000 frames per sec). Contrary to expectation, platelet flow was well mixed in the circulating blood, and did not occur preferentially in the peripheral layer. However, transient contact of platelets with endothelial cells and detachment ( gtouch and go h phenomenon) were occasionally observed in the pial arteries. Flowing platelets in the capillaries were by no means stationary. For documentation of platelet tracking, video clips taken at 250-500 frames per sec for a 10 sec interval were analyzed with KEIO-IS2 (see Schiszler et al. Brain'05). The software automatically assigned individual numbers to platelets, calculated their velocities, and presented the results on a spreadsheet (Excel). The velocities were 2.72 }0.52 mm/sec for arterioles, 0.75 }0.3 mm/sec for single capillaries and 0.21 }0.07 mm/sec for venules. In the later stage of experiments (5-10 min after CSFE injection), platelets began to adhere to the wall of venules, occasionally forming large platelet aggregates, probably owing to some toxic effect of CFSE itself on the endothelial cells. The high-speed laser confocal fluorescence microscope is a promising tool for investigating hemodynamic changes at the vessel wall, including formation of platelet clots and their resolution with therapeutic agents.

Stellate cells release NO and induce vasodilation of intraparenchymal blood vessels in rat cerebellar slices

Stellate cells release NO and induce vasodilation of intraparenchymal blood vessels in rat cerebellar slices

Waterjet Dissection versus Ultrasonic Aspiration in Epilepsy Surgery

Waterjet dissection is currently under close investigation in neurosurgery. Experimentally, precise brain parenchyma dissection with vessel preservation has been demonstrated. Clinically, the safety of the instrument has already been proved. However, precise data demonstrating that waterjet dissection indeed reduces surgical blood loss are still missing. The authors applied the waterjet device in a prospective randomized study in comparison with the ultrasonic aspirator. Because there is little variability in the procedure, 30 patients with temporal lobe epilepsy receiving a tailored temporal lobe resection between December 1999 and October 2002 were selected for this study. Intraoperative vessel preservation, intraoperative blood loss, surgical complications, and epilepsy outcome were evaluated. All patients were followed at 3-month intervals. During surgery, both instruments were easy to handle. Only with the waterjet dissector, however, were even small intraparenchymal blood vessels preserved. Intraoperative blood loss was significantly reduced with the waterjet (mean, 70 +/- 46 ml) compared with the ultrasonic aspirator (mean, 121 +/- 48 ml). However, no difference in the necessity for blood transfusion occurred. No difference was observed with respect to operation time (238.6 +/- 37.0 min with the waterjet, 247.5 +/- 41.5 min with the ultrasonic aspirator), surgical complications, and outcome. The waterjet dissector enables a significant reduction of intraoperative blood loss in the investigated setting. However, further studies are needed to confirm these results with a larger number of patients. Studies also are needed to prove that the reduction of blood loss is of clinical relevance for the outcome of the patients.

Cigarette Smoke Induces Rapid Changes in Gene Expression in Pulmonary Arteries

The pathogenesis of cigarette smoke-induced pulmonary hypertension is not well characterized. We used RT-PCR to examine gene expression of nitric oxide synthase 2 (NOS-2), nitric oxide synthase 3 (NOS-3), endothelin, and vascular endothelial growth factor (VEGF) and its flk-1 receptor (VEGF-R) in main pulmonary arteries and in intraparenchymal arteries microdissected from alcohol-fixed paraffin blocks. The main pulmonary artery and intraparenchymal vessels responded in a similar fashion, with up-regulation of endothelin, VEGF, and VEGF-R gene expression evident by 2 hours after smoke exposure. Up-regulation of gene expression was still present at 24 hours after exposure, and at this time there was also a small increase in NOS-2. As a comparison, we examined the trachea and microdissected intraparenchymal airways and found up-regulation of endothelin and NOS-2 at 2 hours and additional up-regulation of NOS-3 at 24 hours. These findings suggest that the pulmonary vasculature very rapidly responds to cigarette smoke with up-regulation of mediators that control vascular cell proliferation and vascular constriction. These changes support the idea that pulmonary hypertension in cigarette smokers reflects a direct effect of smoke on the vasculature. The pattern of response in the vessels is distinctly different from that in the airways.

The Roy–Sherrington hypothesis: facts and surmises

The 110-year-old metabolic hypothesis of Roy and Sherrington cannot fully explain the increases of cerebral blood flow (CBF) during increased functional activity of the central neurons. CBF may increase (a) much faster than the accumulation of the metabolic end products, (b) out of proportion to metabolic demands, (c) without significant change in local metabolism. The tight coupling of neuronal activity and blood flow in the brain is demonstrated by a large amount of data. Perivascular nerve endings were identified in the outer smooth muscle layer of the pial and intraparenchymal vessels. Their axon terminals contain a large variety of neurotransmitters, often co-localized in synaptic vesicles. Stimulation of the nerves results in a release of transmitters into the 80–100-nm neuromuscular synaptic clefts, and their specific receptors were identified in the vessel wall. There is ample evidence to suggest that neurogenic stimuli via perivascular nerve endings may act as rapid initiators, inducing a moment-to-moment dynamic adjustment of CBF to the metabolic demands, and further maintenance of these adjusted parameters is ensured by the metabolic and chemical factors. The significance of the perivascular nerves in the regulation of the cerebral blood flow, however, is either underestimated or completely neglected in the majority of textbooks for both medical students and clinicians. Since the regulatory role of the nervous system in the cerebrovascular bed has been fully appreciated among investigators in the last decades, revision of this antiquated view of the common medical knowledge is urgent.

Ecotomografía Doppler arterial intrarrenal en pacientes cirróticos con ascitis, con y sin síndrome hepatorrenal

The pathophysiological hallmark of the hepatorenal syndrome (HRS) is renal vasoconstriction. Doppler ultrasonography can be used to assess the vascular resistance in small renal intraparenchymal vessels through analysis of the Doppler waveform by a parameter termed Resistive Index (RI). We postulated that the RI could be important for the diagnosis and prognosis of HRS. To assess the RI in cirrhotic patients with ascites, with and without HRS. We studied 48 cirrhotics with ascites, of whom 12 were with and 36 without HRS and other 23 were normal subjects. We measured the intrarenal arterial RI (Resistive index = Peak systolic velocity - Minimum diastolic velocity/Peak systolic velocity) with color Doppler ultrasonography after visualization of interlobular or arcuate arteries. It was considered abnormal when higher than 0.70. The RI values, mean and SD) were: normal subjects: 0.58 +/- 0.05, cirrhotics with ascites: 0.65 +/- 0.05 and cirrhotics with ascites and HRS: 0.78 +/- 0.11. Patients with HRS had significantly higher values than those without HRS (p < 0.001). The Relative Risk of developing the HRS in patients with a RI > or = 0.70 were 3.32 (CI 95% = 1.79-6.2) The RI was useful in patients with cirrhosis and ascites for the prognosis of HRS and could suggest diagnosis of HRS with values of 0.78 or higher, if other clinical conditions that produce renal vasoconstriction are excluded.

MR Angiography with a New Rapid Clearance Blood Pool Agent (P792): Initial Experience in Rabbits

The T1-shortening effect of gadolinium chelates allows select enhancement of the arterial lumen without depending on time-of-flight effects. This assures maximal contrast between the arterial lumen and surrounding tissues and renders the technique less susceptible to flow dependent artifacts. The extracellular nature of the paramagnetic gadolinium chelates leads to rapid diffusion into the extracellular compartment, resulting in decreasing arterial signal intensity and concomitant enhancement of surrounding tissues. The short intravascular half-life requires optimal timing of the contrast bolus and provides only a very limited time window for data collection during the arterial phase of the intravenously administered contrast bolus. Timing errors may render the examination suboptimal or non-diagnostic. Thus high contrast doses and fast injection rates are required to induce adequate T1-shortening of the blood in the vascular territory under investigation. Contrast dose limitations limit most protocols to a single injection. Repeated imaging is possible only with low dose protocols which require time consuming image subtraction techniques to obtain adequate contrast to noise between vessels and surrounding tissues (1). The desirable concomitant assessment of organ perfusion as a complement to arterial imaging, possibly even prior to and following the application of pharmaceutical stressing agents, is limited by the leakage of the extracellular into the interstitial space. Blood pool contrast agents potentially overcome these limitations. On account of their larger molecular size, they are known to reveal a substantially higher relaxivity (2– 4). Even in the arterial phase they are available in a higher concentration due to less leakage into the pulmonary capillary bed. These factors further reduce the required dose. Furthermore, they allow for equilibrium phase imaging. Furthermore, lack of concomitant soft tissue enhancement permits better visualization of small distal intraparenchymal vessel branches (5–9). In this study we assessed the in vitro signal enhancement characteristics of P792 compared to gadoterate dimeglumine (Gd-DOTA), a representative, market introduced extracellular non-specific agent (NSA).

Asymptomatic versus symptomatic infarcts from vasospasm in patients with subarachnoid hemorrhage: serial magnetic resonance imaging.

By use of serial magnetic resonance imaging (MRI), we prospectively investigated the incidence of and the risk factors associated with infarction caused by vasospasm with or without a delayed ischemic neurological deficit (DIND) in patients with subarachnoid hemorrhage (SAH). In 125 patients who underwent surgery for early aneurysms, postoperative MRI scans were obtained at four time points. We defined an infarct from vasospasm as a new lesion not present on the initial MRI within 3 days after SAH and therefore not attributable to primary brain damage or surgical complications. Overall, symptoms of infarction (i.e., DIND) occurred in 38% of patients (48 of 125); DIND with a new infarct on MRI was evident in 34% (43 patients), whereas 4% (5 patients) showed no new lesion but had a DIND. However, 29 patients (23%) showed a new infarct but no DIND on MRI studies (asymptomatic infarction). Asymptomatic ischemic lesions due to vasospasm tended to involve noneloquent brain areas in the territory of intraparenchymal perforators. Multivariate analysis identified variables associated with symptomatic infarction to be of poor SAH grade, advanced age of the patient, angiographic findings of vasospasm, multiple cortical infarcts on MRI studies consistent with vasospasm, and chronic hydrocephalus. Analysis of the data confirmed the occurrence of asymptomatic infarcts due to vasospasm. These infarcts often developed in noneloquent areas representing perforator territory. MRI investigation of vasospastic lesions referable to intraparenchymal vessels such as perforators complements the study of extraparenchymal major vessel vasospasm in patients with SAH by computed tomographic angiography.

Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) are still controversial and uncertain. The aim of this study was to investigate the changes of cerebral microcirculation during cerebral vasospasm and to clarify the roles of microcirculatory disturbances in cerebral ischemia by measuring cerebral circulation time (CCT) and regional cerebral blood flow (rCBF). In 24 cases with aneurysmal SAH, rCBF studies by single-photon emission CT and digital subtraction angiography (DSA) were performed on the same day between 5 and 7 days after SAH and/or within 4 hours after the onset of delayed ischemic neurological deficits. CCT was obtained by analyzing the time-density curve of the contrast media on DSA images and was divided into proximal CCT, which was the circulation time through the extraparenchymal large arteries, and peripheral CCT, which was the circulation time through the intraparenchymal small vessels. They were analyzed in association with rCBF and angiographic vasospasm. Severe angiographic vasospasm statistically decreased rCBF, and correlation between the degree of angiographic vasospasm and rCBF was seen (r=0.429, P=0.0006). Peripheral CCT showed strong inverse correlation with rCBF (r=-0.767, P<0.0001). Even in none/mild or moderate angiographic vasospasm, prolonged peripheral CCT was clearly associated with decreased rCBF. In addition to the marked luminal narrowing of large arteries detected as severe angiographic vasospasm, microcirculatory changes detected as prolonged peripheral CCT affected cerebral ischemia during cerebral vasospasm. These results suggested that impaired autoregulatory vasodilation or decreased luminal caliber in intraparenchymal vessels may take part in cerebral ischemia during cerebral vasospasm.

Distribution of amyloid beta 42 in relation to the cerebral microvasculature in an elderly cohort with Alzheimer's disease.

Amyloid beta (A beta) deposits and neurofibrillary pathology are characteristic features of Alzheimer's disease (AD). The association of A beta with cerebral vessels is an intriguing feature of AD. While some degree of cerebral A beta angiopathy involving the leptomeninges and intraparenchymal vessels occurs in almost all cases of AD, the proportion of microvessels within a neocortical region containing deposits of A beta peptide is not known. In this study, we examined a cohort of clinically and pathologically evaluated AD cases to assess the percentage of cerebral microvessels in the temporal cortex and parahippocampal gyrus associated with the predominant, A beta 42 form of the peptide. We also assessed whether the distribution and burden of amyloid was related to apolipoprotein E (APOE) genotype. Using double immunostaining methods, we surprisingly found that at least 40% of the microvessels in the two brain regions contained A beta 42 deposits. There was no correlation of such localization with APOE genotype, however, epsilon 4 homozygotes revealed a greater burden of A beta 40. These observations suggest that high proportions of cortical microvessels are associated with A beta 42, which may affect microvascular function.

Peptidergic innervation of human cerebral blood vessels and saccular aneurysms.

Peptidergic innervation of the human cerebral vasculature has not yet been described in detail and its role in the maintenance of cerebral autoregulation still needs to be established. Similarly, few data exist on the innervation of vascular malformations. The aim of this study was to clarify the peptidergic innervation patterns of human cerebral arteries of various sizes, and, for the first time, that of saccular aneurysms. Light microscopic study of whole-mount preparations of human cerebral arteries and aneurysm sacs resected either during tumor removal or after neck-clipping were carried out by means of silver-intensified light microscopic immunocytochemistry visualizing neuropeptide-Y, calcitonin gene-related peptide and substance P immunoreactivity. Systematic morphological investigations confirmed the presence of longitudinal fiber bundles on the adventitia and a network-like deeper peptidergic system at the adventitia-media border, while in smaller pial and intraparenchymal vessels, only sparse longitudinal immunopositive axons could be detected. The innervation pattern was totally absent in the wall of saccular aneurysms with the complete disappearance of peptidergic nerve fibers in some areas. To the best of our knowledge neither the disappearance of this network on small pial and intraparenchymal vessels, nor the absence of an innervation pattern in saccular aneurysms have been described before. Nonhomogeneous peptidergic innervation of the human cerebral vascular tree might be one of the factors responsible for the distinct autoregulatory properties of the capacitance and resistance vessels. Malfunction of this vasoregulatory system might lead to the impairment of autoregulation during pathological conditions such as subarachnoid hemorrhage.

Migraine associated bilateral intracerebral haemorrhages

The authors report a case of bilateral basal ganglionic haemorrhages which occurred during an attack of classical migraine. The patient had a history of migraine associated with aura of neurological deficit for 10 years and a history of arterial hypertension for 20 years, which was treated with propranolol. Intracerebral haemorrhage during an attack of migraine is very rare and up to now the existence of true migraine-induced intracerebral haemorrhage has been controversial. Our case of bilateral occurrence of the haemorrhages supports the theory of the existence of migraine-induced damage of the wall of intraparenchymal vessels during vasoconstriction and focal ischaemia at the beginning of a migraine attack. Subsequent vessel rupture may occur during the following period of increased cerebral blood flow especially with coexisting arterial hypertension. The terminology of the syndrome of migraine associated with intracerebral haemorrhage is reviewed.

Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia

Several growth factors have been implicated in the pathogenesis of Alzheimer's disease (AD). We considered whether the vascular endothelial growth factor (VEGF) is involved in the vascular pathology associated with most cases of AD. We observed enhanced VEGF immunoreactivity in clusters of reactive astrocytes in the neocortex of subjects with AD compared to elderly controls. VEGF reactivity was also noted in walls of many large intraparenchymal vessels and diffuse perivascular deposits. In addition, we established that astrocytic and perivascular VEGF reactivity was enhanced in cerebral cortex of rats subjected to cerebral ischemia and to chronic hypoxia; experimental conditions known to be associated with astrogliosis and angiogenesis. We suggest the increased VEGF reactivity, also observed in infarcted human brain tissue, implicates compensatory mechanisms to counter insufficient vascularity or reduced perfusion (oligemia) apparent in AD.

Expression of endothelin(A) receptors in human gliomas and meningiomas, with high affinity for the selective antagonist PD156707.

Endothelin (ET) immunoreactivity, ET production, and specific ET receptors have been identified in the brain. Changes in ET concentration or receptor expression have been implicated in the pathophysiological changes in vasospasm after subarachnoid hemorrhage and in cerebral neoplasia. In this study, we have characterized the ET(A) and ET(B) receptor subtypes present in human normal cerebral cortex (NCC) and two common central nervous system tumors, i.e., meningioma (MNG) and glioblastoma multiforme (GBM). A knowledge of the ET receptor subtypes present may provide a novel therapeutic target for newly developed ET antagonists. Saturation, competition, and autoradiographic studies were performed with the subtype-specific radioligands 125I-PD151242 and 125I-BQ3020, to characterize the ET(A) and ET(B) receptors present in NCC, MNG, and GBM. NCC expresses high-affinity ET(A) receptors on pial and intraparenchymal vessels and high-affinity ET(B) receptors on glia and neurons. MNGs express mainly (85%) high-affinity ET(A) receptors in a diffuse pattern, whereas GBMs express high-affinity ET(A) receptors on the neovasculature and ET(B) receptors on the nonvascular elements. The ET antagonist PD156707 (Kd = 0.059 nmol/L) showed a higher affinity for the ET(A) receptor subtype than did bosentan (Kd = 1.1 nmol/L). ET(A) receptors are expressed in high concentrations in MNGs and in the vasculature of NCC and GBMs. The ET(A)-selective antagonist PD156707 may be of potential therapeutic value in vascular and neoplastic diseases of the central nervous system.

Subcortical vascular dementia: Therapeutical aspects

Summary A large number of drugs have been or are being currently tested in vascular dementia (VaD) but so far no conclusive evidence has been achieved. Secondary prevention measures, such as control of arterial hypertension and other risk factors, still appear to be the sole approach with some efficacy. Unsuccessful results of trials testing agents aimed at improving the cognitive function and to ameliorate the disease course may stand, at least in part, on the heterogeneity of pathophysiological mechanisms underlying VaD. Therefore, trials testing drugs presumed to be active in VaD should focus on specific pathological subgroups of patients, such as those with subcortical forms. These latter are mainly caused by small intraparenchymal vessel changes leading to focal ischemic damage (lacunar infarcts) in the deep hemisphere structures and to diffuse suffering of subcortical white matter. Calcium-antagonists are drugs that inhibit the intracellular influx of calcium. The alteration of calcium homeostasis is believed to be involved in both cerebral ischemia and aging, hence the possible role of these compounds in the therapy of age-related forms of dementia. The best known calcium-antagonist that crosses the blood-brain barrier and is active in the central nervous system is nimodipine. The rationale for the use of nimodipine in subcortical VaD stems on its action on small vessels. We recently evaluated in a preliminary open trial the efficacy and safety of nimodipine in thirty-one patients with dementia and brain computed tomography images consistent with subcortical VaD. A significant improvement in the total score and in all the items of the San doz clinical assessment geriatric scale (SCAG) was observed throughout the study period. A multi-center, international, randomized, placebo-controlled trial with nimodipine in subcortical VaD is in progress.

Anatomical and surgical aspects of splenic segmentectomies

Based upon the anatomicosurgical segments of the spleen, suggested by DiDio and demonstrated in cadavers, classified and named by Neder (1958) and Zappalá (1958, 1959, 1963), the normal segmental organization was anatomically and radiologically confirmed in 51 human spleens, after studying corrosion casts and radiograms of intraparenchymal vessels (Christo, 1959 a, b, 1960, 1962, 1963, 1993). From 1958 to 1965, pioneer segmental resections were performed successfully in 34 dogs and in 9 patients to safely remove traumatic injured splenic segments. At the same time, the overwhelming postsplenectomy infection (OPSI) became well identified. Consequently, to save normally functioning splenic parenchyma became the most important issue in the management of splenic injuries. The anatomical basis for partial splenectomy and splenic segmentectomy is discussed. The term "splenorrhaphy" was employed to designate all conservative or parenchyma saving operations of spleen based upon its vascular supply: from topical packings to splenic sutures including "cappings" and partial splenectomies. From analysis of 38 consecutive reports in 20 years, covering 4,076 patients, it was concluded that "splenorrhaphies" had been electively employed in 46% of the injuries and partial splenectomies were identified in 8.6% of these surgical interventions. However, the critical minimal mass of splenic tissue to be preserved after partial splenectomies is still to be defined. Postoperative complications directly related to "splenorrhaphies" are rare. Uncommonly performed after splenectomies, the heterotopical splenic autotransplantation has presented dubious results. Trials with nonoperative management of splenic blunt trauma injuries have been safer among children, whose spleens are predominantly transversally disrupted and have a higher relationship "capsular resistance/parenchymal bulk". Splenectomies have been most frequently the ultimate result of delayed laparotomy and underlying risks of growing blood requirements may surpass the advantages of preventing OPSI.

Morphological changes of intraparenchymal arterioles after experimental subarachnoid hemorrhage in dogs.

Morphological and microcirculatory changes in intraparenchymal vessels after subarachnoid hemorrhage (SAH) have not yet been fully clarified. We conducted this experimental study to investigate the serial morphological changes of intraparenchymal arterioles after SAH. SAH was produced by injecting autologous arterial blood into the cisterna magna twice at 48-hour intervals in 30 dogs. The dogs were killed 3, 7, or 14 days after SAH, and then perfusion-fixed specimens of both anterior sylvian giri were obtained by using two methods. Microvascular corrosion casts produced by arterial injection of polyester resin were examined using scanning electron microscopy, and the widths of 40 arterioles of each animal were measured. Sectioned slices from the brain surface to 500 microns deep were examined by light microscopy, and external diameter, internal diameters, and wall thickness of the arterioles at depths of 50, 200, and 500 microns from the brain surface were morphometrically evaluated in 40 arterioles of each animal. In control animals receiving cisternal injections of mock cerebrospinal fluid (n = 10) and in healthy control animals (n = 10), the same examination and evaluation were performed. Corrosion casts of arterioles showed tapered narrowing with folding after SAH, and the width of the arterioles significantly decreased 3 and 7 days after SAH (P < 0.01). Morphometric examination by light microscopy showed a significant decrease of internal diameter of arterioles associated with a significant increase of wall thickness at any depth from the brain surface 3 and 7 days after SAH (P < 0.05 or P < 0.01). These findings improved 14 days after SAH. Control animals receiving cisternal injections of mock cerebrospinal fluid showed no significant differences compared with healthy control animals. These results suggest that constriction of intraparenchymal arterioles occurs after SAH and may contribute to delayed cerebral ischemia.

Innervation pattern of guinea pig pulmonary vasculature depends on vascular diameter.

The pulmonary vasculature is supplied by various neurochemically distinct types of nerve fibers, including sensory substance P-containing and autonomic noradrenergic, nitrergic, and cholinergic axons. Pharmacological experiments have suggested that various segments of the pulmonary vascular tree respond differently to the respective neuromediators. We, therefore aimed to determine histochemically and immunohistochemically for each of these neurochemically distinct perivascular axons their quantitative distribution along the vascular tree from the extrapulmonary trunks to the smallest intraparenchymal ramifications in control guinea pigs (n = 5). Generally, arterial innervation was more developed than that of veins. Along the arterial tree, noradrenergic and substance P-containing axons were ubiquitous from the pulmonary trunk to smallest intraparenchymal vessels, whereas nitrergic axons were practically restricted to large (> 700-microns) extrapulmonary arteries. Cholinergic axons were regularly present at arteries down to 100 microns in diameter and innervated two-thirds of small arteries (50-100 microns). The results demonstrate that the noradrenergic vasoconstrictor innervation extends throughout the pulmonary vascular system whereas the innervation pattern with various types of vasodilator fibres changes with vascular diameter, parallel to known pharmacological differences in cholinergic and nitrergic vasodilator effects.

Abundance of the longer A beta 42 in neocortical and cerebrovascular amyloid beta deposits in Swedish familial Alzheimer's disease and Down's syndrome.

Recent studies have demonstrated the deposition of amyloid beta (A beta) protein with carboxyl- and aminoterminal heterogeneity in cortical and cerebrovascular deposits of Alzheimer's disease (AD). Using carboxyl end-terminal specific antibodies to A beta peptides, we examined the immunocytochemical distribution of A beta 40 and A beta 42 species in brain tissue from a Swedish subject with familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid beta precursor protein (A beta PP), and from subjects with Down's syndrome and sporadic AD. In the Swedish subject, we found profound parenchymal A beta deposits and cerebral amyloid angiopathy in all four cortical lobes and cerebellum. A beta 42 was evident in almost all parenchymal deposits as well as many vascular deposits. Although A beta 40 was present in meningeal and intraparenchymal vessels, deposits containing this shorter peptide reactivity were sparse. Surprisingly, our observations in Swedish FAD showing a remarkable abundance of A beta 42 in both parenchymal and vascular deposits were qualitatively similar to the Down's syndrome and most sporadic AD cases, and to previously published A beta PP717 FAD. While previous transfection studies in different cell cultures indicate substantially increased soluble A beta production and A beta 40 species to be predominant, it would appear that the double A beta PP mutations in Swedish FAD largely result in the deposition of the longer A beta 42 in vivo.