Transition of research focus from vasospasm to early brain injury after subarachnoid hemorrhage

Abstract

Subarachnoid hemorrhage is a devastating disease that can be difficult to manage. Not only is the initial bleeding and rebleeding associated with high mortality, but a large fraction of patients also develop a delayed neurological deficit even when the aneurysm was successfully secured with clipping or coiling. Past research effort has traditionally been focused on vasospasm, which was conceived to be the sole factor for delayed neurological deficit. The failure of anti-vasospastic drugs to improve outcome in clinical trials has brought into focus the significance of early brain injury. The immediate events associated with subarachnoid hemorrhage, including increased intracranial pressure, decreased cerebral blood flow and global ischemia initiate a cascade of pathological changes that occur before the onset of delayed vasospasm. These pathological changes in the very early stage of the hemorrhage propagate and cause blood-brain barrier disruption, inflammation, oxidative stress and cell death. Focusing only on the treatment of vasospasm with complete disregard for early brain injury is insufficient for the management of subarachnoid hemorrhage. Instead, a therapeutic intervention has to aim at stopping the molecular cascades of early brain injury that may lead to long-term deficits in addition to vasospasm. We review the pathological mechanisms of early brain injury, which may reveal new therapeutic avenues that can be exploited to serve as combination therapy with anti-vasospasm medications in the future. Keywords: delayed ischemic neurological deficit, early brain injury, subarachnoid hemorrhage, vasospasm.

Early Cortical Thickness Change after Mild Traumatic Brain Injury following Motor Vehicle Collision

“…58,[66][67][68] Acute hypoperfusions are attributed to reversible microvasoconstriction in a rat model of mTBI, 69 and acute vasoconstriction has been reported within an hour after TBI in human survivors with subarachnoid hemorrhage. 70,71 Further, even transient hypoperfusion may produce prolonged changes in cortical thickness as evidenced by decreased cortical thickness and less fMRI activation in rats at 4 months after a single episode of hypoxia-ischemia. 72 Future studies that simultaneously measure cortical thickness and perfusion at an early stage after mTBI may shed light on this relationship.…”

Deficiency of tenascin-C and attenuation of blood-brain barrier disruption following experimental subarachnoid hemorrhage in mice

“…3 In a clinical setting as well, brain edema on CT was reported to be an independent risk factor for mortality and poor outcome following SAH. 5 Many molecules, such as blood breakdown products and inflammatory mediators, may be involved, either acting simultaneously or at different stages during BBB disruption.…”

“…Neurological scores (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) were assessed by summing 6 test scores (spontaneous activity; spontaneous movement of 4 limbs; forepaw outstretching; climbing; body proprioception; and response to whisker stimulation), as previously described. 8 A beam balance test investigated the animal's ability to walk on a narrow wooden beam for 60 seconds: 4 points, walking ≥ 20 cm; 3 points, walking ≥ 10 cm but < 20 cm; 2 points, walking ≥ 10 cm but falling; 1 point, walking < 10 cm; and 0 points, falling while walking < 10 cm.…”

Early Systemic Procalcitonin Levels in Patients with Aneurysmal Subarachnoid Hemorrhage

“…More recently, mechanisms of early brain injury have moved center stage in the research focus. It has been suggested that these mechanisms evolve with time and contribute to the path-ogenesis of DCI [3,4]. The rupture of an aneurysm and consequent release of blood into the subarachnoid space leads to an abrupt increase of the intracranial pressure (ICP), which is suggested to cause a brief cerebral perfu-sion arrest [4].…”