Academic literature on the topic 'Emorragia subaracnoidea'

Viene presentato un caso di emorragia subaracnoidea sine materia con TC che dimostra un caratteristico sanguinamento nelle cisterne perimesencefaliche. L'ESA con angiografia negativa è una patologia abbastanza frequente (la sua incidenza varia tra il 7% e il 28% di tutte le emorragie subaracnoidee)1–4: alla TC la sede e la quantità dello stravaso ematico potrebberro forse essere considerate caratteristiche e si differenziano dall'emorragia da rottura di aneurisma. Anche se la TC può assumere un ruolo predittivo, è assolutamente necessario ancora oggi procedere ad uno studio angiografico completo e ineccepibile5. In questi casi di ESA con sanguinamento perimesencefalico e angiografia negativa, come viene riportato in letteratura, il decorso clinico è favorevole4.

Early activation of inflammation in an experimental model of subarachnoid hemorrhage Introduction. There is increasing evidence that inflammation plays a critical role in the pathogenesis of vasospasm and delayed ischemic deficits after Subarachnoid Hemorrhage (SAH). Objective. Aim of this study is to evaluate the early activation of inflammatory response at the level of basilar artery in a model of single hemorrhage in rats. Material and Methods. A single hemorrhage model was used. CD-IGS rats (250-350 gr) were anesthetized using an i.p. administration of ketamine (100mg/Kg) and midazolam (1 mg/Kg) and subcutaneous fentanyl (0.0075 mg) to control pain. In SAH group, subarachnoid hemorrhage was induced by injection of autologous arterial blood into the cisterna magna of the animal throughout a suboccipital puncture (200 µl in 3 min). Animals were therefore maintained with the head down for 15 minutes and were leaved to breath autonomously and to recover. In Sham group, rats were submitted to the same procedures, puncturing the cisterna magna, without injecting arterial blood in it. In basal group, rats were not submitted to any surgical procedure. In short term experiments, animals were sacrificed 4 hours after the puncture. Basilar artery was then removed from the rat brain and freezed. A pool of 3 arteries were necessary in order to obtain adequate amount of RNA to perform gene expression analysis. 4 pool of arteries for each group was submitted to a real-time PCR analysis to evaluate expression of the following genes: TNF-α, IL-6, CXCL-1, iNOS, ET-1, ICAM-1. 3 pools of arteries for each group were submitted to TaqMan Low Density Array. TaqMan Low Density Array is a consumable consisting of 384 wells connected by a series of microfluidic channels, designed to be used on the Applied Biosystems 7900HT Fast Real-Time PCR System platform. Microfluidic technology allows multiple targets to be analyzed across many samples simultaneously. These arrays are used to analyze specific biological pathway activation and the expression of genes of interest. In this work, 90 genes of interest related to the inflammatory response, oxidative stress, repair mechanisms and apoptosis, and 7 genes of reference were analyzed. In long term experiments, rats were divided in 2 groups: SAH group and basal group. In SAH group, animals were sacrificed 5 days after procedure or at the occurrence of any clinical disturbances. At sacrifice animals were perfused with isotonic phosphate-buffered saline (PBS) and fixed with paraformaldehyde. Brain was therefore removed and freezed in a solution of OCT, isopentane and liquid nitrogen. Section of 20 m were performed in the brain stem of the rats, in order to complete a morphometric analysis (diameter, area, thickness) of the basilar artery at three levels. Results. Preliminary analysis of genes expression with RT-PCR showed the early up-regulation of all genes in the SAH group: TNF-α (SAH 3.2, SHAM 2.2, CONTROL 1.1), IL-6 (SAH 343, SHAM 2, CONTROL 1); CXCL-1 (SAH 187, SHAM 42, CONTROL 1), iNOS (SAH 39, SHAM 2, CONTROL 0), ET-1 (SAH 2.6, SHAM 1.2, CONTROL 1.1), ICAM-1 (SAH 5.1, SHAM 1.8, CONTROL 1.1). Subsequent analysis with Taqman Low Density array allowed to confirm the clear differentiation of the SAH group with respect to the basal and SHAM groups (p=0.0370). With the assistance of the software EASE, the analysis was deepened in order to evaluate the hypothetic modulation of molecular processes in SAH group. This demonstrated an up-regulation of genes involved in different aspects of immune response, response to stress or external stimulus, and tissue repair, while genes coding for structural protein of intercellular junction or localized at the level of cell membrane are down-regulated. Morphometric analysis in long-term experiments showed the reduction of basilar artery diameter and area in the SAH group (55 ± 15 microm vs 91 ± 20 microm and 1381 ± 150 microm2 vs 3898± 214 microm2). Conclusions These results show an early expression of genes involved in inflammatory process on the wall of the intracranial vessels exposed to subarachnoid blood injection in a model of single hemorrhage in rats. This seems to confirm that inflammation plays a crucial role in the cascade of events after SAH, leading to vasospasm and delayed ischemic deficits, and suggests that new treatments capable to modulate this response could eventually be beneficial.

TITLE: Subarachnoid Hemorrhage: cognitive evaluation and 3T MRI imaging in the acute phase; preliminary results AUTHOR: Giulio Andrea Bertani ABSTRACT INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) is a cerebrovascular disease characterized by high mortality and severe complications, in particular hydrocephalus and vasospasm. Traditional imaging techniques and outcome assessment scales (GOS, MRS) are unable to clarify the complex pathophysiological mechanisms of the disease or to adequately evaluate the impact on cognitive functions. AIMS: To investigate patients in the acute phase after SAH by advanced neuroimaging techniques (MRI) and in-depth neuropsychological evaluations, in order to assess acute cognitive deficits and to connect them to the numerous clinical and radiological variables which affect the course of the disease. METHODS: In the setting of a larger ongoing observational study, we selected 23 adult patients suffering from aneurysmal SAH. Following aneurysm treatment (clipping or coiling), patients underwent 3T brain MRI with MRA within 48 hours and 7-10 days, using a dedicated protocol; in the same times patient underwent neuropsychological assessments for language, memory, executive functions, praxis, orientation and personal autonomy. Monitoring of arterial flow by means of Transcranial Doppler (TCD) was performed. RESULTS: the majority of patients had marked cognitive deficits in all areas examined after SAH, with only marginal improvements at time 2. Early MRI showed ischemic volumes of less than 2 ml in 17 cases, between 2 and 10 ml in 3 and greater than 10 ml in 1; at T2 6 new lesions were detected, 5 less than 2 ml and 1 between 2 and 10 ml. The neuropsychological assessments showed multiple relationships with clinical and radiological parameters, location and side of the aneurysm, hydrocephalus and vasospasm; the correlation with ischemic lesions showed contradictory results. CONCLUSIONS: This study documents the pronounced cognitive impairment following SAH, despite a modest load in terms of ischemic lesions detected by MRI. It confirms that some features of the disease, such as the location and lateralization of the aneurysm, and the type of treatment have a deep influence on cognitive performances in the short term. This research also puts the basis for future selection of a battery of tests specifically designed to detect early subtle neuropsychological abnormalities, which are often associated with severe complications of SAH.

Background: L'emorragia subaracnoidea (ESA) è una condizione patologica caratterizzata da un accumulo di sangue nello spazio subaracnoideo conseguente a trauma cranico o rottura di un aneurisma. Il decorso clinico è gravato da complicanze cerebrovascolari e sistemiche che peggiorano significativamente la prognosi del paziente. La complicanza più comune e grave dell’ESA è il vasospasmo dell’arteria basilare, che può causare ischemia cerebrale. L'intensa reazione infiammatoria che si sviluppa nello spazio subaracnoideo costituisce un importante fattore patogenetico del vasospasmo. Le complicanze periferiche infettive e infiammatorie,assai frequenti in pazienti con ESA, sembrano essere anche una conseguenza diretta del danno cerebrale. Infatti, il rilascio di citochine nel SNC attiva in modo incontrollato l’asse ipotalamo-ipofisi-surrene, il sistema nervoso simpatico e la via anti-infiammatoria colinergica. Ciò causa l’induzione di uno stato di immunodepressione che aumenta la suscettibilità dell'organismo alle infezioni. Contemporaneamente, nei tessuti periferici, si verifica l'attivazione della risposta flogistica e dell’infiltrazione leucocitaria. Ad oggi, non esiste ancora una strategia risolutiva per il trattamento dell’ESA. Le melanocortine potrebbero costituire un'opportunità terapeutica innovativa. Tali peptidi, derivati dal precursore pro-opiomelanocortina, sono rappresentati principalmente dall’l'ormone -melanocitostimolante (-MSH) e dalll'adrenocorticotropina (ACTH). Essi esercitano potente attività anti-infiammatoria, anti-piretica e immunomodulante. Gli effetti delle melanocortine si esplicano attraverso la modulazione dell’espressione di mediatori pro-infiammatori e l’attivazione di circuiti neurali immunomodulanti endogeni. Obiettivi Della Ricerca: L'obiettivo generale è proporre un nuovo approccio terapeutico per il trattamento dell’ESA. Gli scopi specifici erano: A) Identificare e caratterizzare le modificazioni molecolari indotte a livello dell'arteria basilare e negli organi periferici (milza, fegato e intestino) durante ESA sperimentale; B) Valutare l'efficacia della terapia con una melanocortina sintetica nel prevenire o attenuare le alterazioni associate all'ESA. Lo studio è articolato in 3 fasi: 1) Sviluppo del modello di ESA nel ratto; 2) Analisi molecolare delle ripercussioni precoci e tardive nell’arteria basilare e in periferia; 3) Valutazione dell’efficacia terapeutica delle melanocortine. Risultati: Ottimizzazione e standardizzazione della procedura basata su singola iniezione di sangue autologo in cisterna magna per indurre l’ESA nel ratto. L’analisi di gene profiling indica che l’ESA induce già a 4 ore una profonda alterazione del profilo di espressione dell’arteria basilare. La valutazione del calibro dell'arteria a 5 giorni mostra una riduzione del diametro vascolare del 50%. I risultati preliminari in organi periferici forniscono indicazioni circa la capacità dell’ESA di attivare una risposta extracerebrale e incoraggiano il proseguimento della ricerca allo scopo di caratterizzare in maniera più approfondita tale fenomeno. Il trattamento sistemico con la melanocortina sintetica NDP-MSH ha prevenuto molte delle alterazioni indotte dall’ESA nell’arteria basilare. L’effetto protettivo sembra essere esercitato attraverso la modulazione di diverse vie di segnalazione. NDP-MSH ha ridotto significativamente la vasocostrizione dell’arteria basilare a 5 giorni post-ESA.
Background: Subarachnoid hemorrhage (SAH) is a pathological condition caused by bleeding into the subarachnoid space. Central and peripheral complications worsen patient outcome. Vasospasm is a severe central complication of SAH. It can cause ischemia and permanent brain damage or death. Bleeding-induced inflammation in the subarachnoid space contributes to vasospasm pathogenesis. In addition, peripheral organs develop inflammatory and infectious complications that seem to be a direct consequence of central injury. Indeed, cytokine production induced by brain damage causes activation of hypothalamic-pituitary-adrenal axis, sympathetic nerve signalling and cholinergic anti-inflammatory pathway. These signals induce immunodepression that could partly account for SAH-related increased susceptibility to infection. In peripheral tissues, activation of 2-adrenoreceptors triggers local inflammatory response and leukocyte recruitment. No consistently efficacious therapies have been identified and implemented in clinical practice for this dire condition. Treatment with melanocortins could constitute an innovative therapeutic strategy. Melanocortin peptides, such as -melanocyte-stimulating hormone (-MSH) and adrenocorticotropic ormone (ACTH), are pro-opiomelanocortin derivatives that exert potent anti-inflammatory, immunodulatory, and antipyretic action. These molecules can directly modulate expression of pro-inflammatory molecules in responsive cells and activate endogenous anti-inflammatory neural circuits. Objectives: The general aim in the present research is to implement a novel therapeutic approach for SAH treatment. Specific goals were: A) To identify and characterize SAH-induced molecular alterations in the basilar artery and in the spleen, large intestine and liver; B)To evaluate whether melanocortin treatment can attenuate SAH-associated central and peripheral complications. The present research is divided in 3 phases: 1) Development of an experimental model to induce SAH in the rat; 2) Analysis of SAH-associated molecular alterations in the basilar artery and in peripheral organs at 4 hours and 5 days post-hemorrhage; 3) Evaluation of the potential protective action of melanocortin treatment. Results: Optimization and standardization of surgical procedure based on single autologous blood injection into the cisterna magna to induce SAH in the rat. Gene profiling analysis indicates that SAH induced a profound gene expression alteration in the basilar artery at 4 h. Morphometric analysis shows a marked vasoconstriction in the basilar arteries from the SAH group relative to controls. Preliminary data indicate that hemorrhage exerts detrimental effects in the spleen and liver. Further investigations are required to better analyze peripheral consequences of central injury. Systemic administration of the synthetic melanocortin NDP-MSH prevented most of SAH-induced alterations in the basilar artery. Protective effect is exerted through modulation of different signaling pathways. In addition, NDP-MSH significantly attenuated basilar artery vasoconstriction at 5 days post-SAH.