Background and Significance: Subarachnoid haemorrhage (SAH) is a cerebrovascular emergency due to an intracranial aneurysm rupture associated with significant mortality. Within survivors, 50% remains severely disabled. SAH can be considered an ischemic disease. In fact, the abrupt discharge of blood into the basal cisterns raises the intracranial pressure and reduce cerebral blood flow with early cerebral ischemia (EBI). Later in the course of the disease, many complications affect brain and contribute to a delayed cerebral ischemia (DCI). Among those: hydrocephalus, intracranial hypertension, seizures and vasospasm (VS) above all.VS refers to the arterial narrowing and occurs in 50-70% of patients. Oxy-hemoglobin in Cerebral spinal fluid CSF triggers changes in the intimal and medial part of the arterial wall leading to VS. However DCI and VS are not synonymous and other inflammatory process are implicated in the pathogenesis of DCI. To date, definite Biomarkers associated to early and late ischemia in SAH are still lacking. TGF beta 1 is a highly researched and promising cytokine in the fields of cancer, autoimmune diseases and infectious disease and has multiple roles with effects on cell proliferation, differentiation, morphogenesis, tissue homeostasis and regeneration. TGF beta has been investigated pathologies affecting central nervous system but not fully in SAH. Scope of the study: To disclose the expression of TGF beta in plasma and CSF of SAH patients. To investigate if a temporal profile during EBI and DCI is associated to neurological outcome. Methods: Prospective study. Population: adult patients admitted to the Neurocritical Care Unit at San Gerardo Hospital, suffering from SAH. CSF and plasma samples were drawn at three time points from time of aneurysm rupture within 1 week from admission (T01-day, T1-day 3, T2-day 7). TGF beta was analysed with ELISA KIT, Emax® ImmunoAssay to detect the biologically active TGFβ1. Patients were treated as per standard clinical protocols. Clinical records, drugs, radiological investigations and daily transcranial doppler were recorded. Results: TGF showed a clear trend of expression in CSF ad plasma in all patients with a peak at T0, than reduced on T1 when patients are clinically stable, and then peaked again on T2. Patients who developed cerebral vasospasm showed major increment of TGF beta in CSF compared to blood on T2. Conclusions and future perspectives: This study confirmed a trend in TGF expression and showed that in patients with VS the CSF expression was increased compared to blood at T2, time when VS typically occurs. This study is original and carry the possibility to translate laboratory findings to clinical practice making the TGF beta a possible early marker of DCI with the potential to stratify patients for risk categories. expected advantage i to identify predisposed patients to a more severe course of SAH

(2017). TGF beta expression in plasma and cerebral spinal fluid following subarachnoid hemorrhage (SAH). The potential of the discriminative power associated to early delayed ischemic injury. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2017).

TGF beta expression in plasma and cerebral spinal fluid following subarachnoid hemorrhage (SAH). The potential of the discriminative power associated to early delayed ischemic injury

ABATE, MARIA GIULIA
2017

Abstract

Background and Significance: Subarachnoid haemorrhage (SAH) is a cerebrovascular emergency due to an intracranial aneurysm rupture associated with significant mortality. Within survivors, 50% remains severely disabled. SAH can be considered an ischemic disease. In fact, the abrupt discharge of blood into the basal cisterns raises the intracranial pressure and reduce cerebral blood flow with early cerebral ischemia (EBI). Later in the course of the disease, many complications affect brain and contribute to a delayed cerebral ischemia (DCI). Among those: hydrocephalus, intracranial hypertension, seizures and vasospasm (VS) above all.VS refers to the arterial narrowing and occurs in 50-70% of patients. Oxy-hemoglobin in Cerebral spinal fluid CSF triggers changes in the intimal and medial part of the arterial wall leading to VS. However DCI and VS are not synonymous and other inflammatory process are implicated in the pathogenesis of DCI. To date, definite Biomarkers associated to early and late ischemia in SAH are still lacking. TGF beta 1 is a highly researched and promising cytokine in the fields of cancer, autoimmune diseases and infectious disease and has multiple roles with effects on cell proliferation, differentiation, morphogenesis, tissue homeostasis and regeneration. TGF beta has been investigated pathologies affecting central nervous system but not fully in SAH. Scope of the study: To disclose the expression of TGF beta in plasma and CSF of SAH patients. To investigate if a temporal profile during EBI and DCI is associated to neurological outcome. Methods: Prospective study. Population: adult patients admitted to the Neurocritical Care Unit at San Gerardo Hospital, suffering from SAH. CSF and plasma samples were drawn at three time points from time of aneurysm rupture within 1 week from admission (T01-day, T1-day 3, T2-day 7). TGF beta was analysed with ELISA KIT, Emax® ImmunoAssay to detect the biologically active TGFβ1. Patients were treated as per standard clinical protocols. Clinical records, drugs, radiological investigations and daily transcranial doppler were recorded. Results: TGF showed a clear trend of expression in CSF ad plasma in all patients with a peak at T0, than reduced on T1 when patients are clinically stable, and then peaked again on T2. Patients who developed cerebral vasospasm showed major increment of TGF beta in CSF compared to blood on T2. Conclusions and future perspectives: This study confirmed a trend in TGF expression and showed that in patients with VS the CSF expression was increased compared to blood at T2, time when VS typically occurs. This study is original and carry the possibility to translate laboratory findings to clinical practice making the TGF beta a possible early marker of DCI with the potential to stratify patients for risk categories. expected advantage i to identify predisposed patients to a more severe course of SAH
CITERIO, GIUSEPPE
ischemia, subarachnoid haemorrhage, TGF beta
MED/41 - ANESTESIOLOGIA
English
Scuola di Dottorato in Medicina Traslazionale e Molecolare
SCUOLA DI DOTTORATO IN MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 72R
28
2015/2016
(2017). TGF beta expression in plasma and cerebral spinal fluid following subarachnoid hemorrhage (SAH). The potential of the discriminative power associated to early delayed ischemic injury. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2017).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/176760
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