It would seem, therefore, that a breakdown in the current ‘drug development pipeline’ exists for ICH. One reason for the current lack of specific treatments in ICH may be due, in part, to specific limitations associated with the most commonly used existing pre-clinical models of the disease, including constraints related to generating spontaneous brain haemorrhages, difficulties in observing brain pathologies in live animals and sub-optimal experimental study design. Therefore, ICH treatment is focussed on quick diagnosis followed by reversal of anticoagulants, blood pressure management and surgery in carefully selected patients as determined by guidelines for the management of spontaneous ICH. There is still, however, a complete lack of specific treatments available to improve outcomes following ICH, despite many drugs showing efficacy in preclinical models. Key modifiable risk factors for ICH are well recognised, and addressing these can reduce incidence. Knowledge of the molecular pathophysiology surrounding haemorrhagic stroke has vastly increased in recent years, with a plethora of reviews describing the primary and secondary injury phases. ICH has a mortality rate of 40% at 1-month post-ictus, coupled with a higher loss of disability adjusted life years, exceeding that of ischaemic stroke despite lower prevalence. The most devastating sub-type of stroke, intracerebral haemorrhage (ICH), accounts for 10–20% of all strokes in high-income countries, whilst incidences increase in central and East Asia and sub-Saharan Africa. Stroke is the second highest cause of death worldwide, surpassed only by ischaemic heart disease. Embracing multidisciplinary collaboration between pre-clinical and clinical ICH research groups will be essential to ensure the success of this type of approach in the future.
#Knockdown stitch sew what pro verification#
Furthermore, we highlight that post-mortem/ex-vivo ICH patient material is a precious and underused resource which could play an essential role in the verification of experimental results prior to consideration for further clinical investigation.
We propose that to increase our chances of successfully identifying new therapeutics for ICH, a bi-directional, 2- or 3-pronged approach using more than one model species/system could be useful for confirming key pre-clinical observations. Here, we review the most commonly used pre-clinical models of ICH and discuss their advantages and disadvantages in the context of translational studies.
It would seem that a breakdown in the ‘drug development pipeline’ currently exists for translational ICH research which needs to be urgently addressed. One reason for this may be related to particular limitations associated with the current pre-clinical models of ICH, leading to a failure to translate into the clinic. Apart from acute and chronic blood pressure lowering, we have no specific medications to prevent intracerebral haemorrhage (ICH) or improve outcomes once bleeding has occurred.