Spreading waves of transient and prolonged decreases in water diffusion after subarachnoid hemorrhage in rats

Abstract

Diffusion-weighted MRI (DWI), which can detect cortical spreading depressions (SDs) as propagating waves of reduced apparent diffusion coefficient (ADC) of water, was used to investigate whether spreading depression occurs after subarachnoid hemorrhage (SAH) induced by endovascular perforation in the rat. Eleven rats underwent SAH while positioned in the magnet. The ADC measurements had a temporal resolution of 12 sec. Transient decreases in ADC to 74 ؎ 5% of pre-SAH values were observed in three rats after SAH, which propagated over the cortex with an average speed of 4.2 ؎ 0.6 mm/min, consistent with an SD wave. Furthermore, in all 11 rats, a wavefront of reduced ADC, which did not resolve within the 12 min observation period, spread at a speed of 3.2 ؎ 1.7 mm/min in the ipsilateral cortex, and again is consistent with the speed of SD propagation. Therefore, spreading depression-like cellular depolarization is a consequence of acute subarachnoid hemorrhage in rats. Subarachnoid hemorrhage (SAH) is a devastating disease, yet little is known about how SAH impacts the brain acutely. Recent interest in the acute phase of SAH is stimulated by the anticipation of a variety of neuroprotective treatments. Therefore, it is important to understand the mechanisms of brain injury during SAH and efforts have been made to elucidate the immediate hemodynamic and cellular responses. There is a transient decrease in cerebral blood flow and a reduction in cerebral oxygen metabolism during the first minutes of SAH (1). Induction of hsp70, a heat-shock protein that is a sensitive marker of neuronal injury and expression of immediate early genes such as c-fos and c-jun is stimulated in rat brain within hours after SAH (2,3). Interestingly, the noncompetitive N-methyl-Daspartate (NMDA) receptor antagonist MK-801 blocked expression of c-fos and c-jun mRNA in the cerebral cortex after SAH (3). Furthermore, decreases in the electroencephalogram (EEG) activity (4 -6) and delays in sensory conduction, measured using somatosensory-evoked potentials (7), have been observed within minutes of SAH.The aforementioned results demonstrate that there are marked deleterious effects on the brain immediately after SAH. Some of the results, notably the blockage of gene expression by MK-801, which is known to suppress spreading depressions (SDs), and the periodic reduction of the EEG amplitude, indicate that spreading depression may play a role in the pathophysiology of acute SAH. Spreading depression refers to a wave of cell depolarization that propagates through the brain tissue at speeds of ϳ3-4 mm/min (8), participating in the cortical response to other noxious stimuli to the brain such as focal cerebral ischemia or trauma (9) in animal models. To the best of our knowledge, however, its occurrence after SAH has not been reported.Magnetic resonance imaging (MRI) is able to noninvasively detect spreading depressions with good spatial and temporal resolution (10,11). In particular, diffusionweighted MRI (DWI) detects spreading depression as propagat...

Measurement of distinctive features of cortical spreading depolarizations with different MRI contrasts

“…The observed 20% decline in tissue ADC during SDs is in line with earlier observations (13,14,18,60) and has been attributed to transient cell swelling due to the temporarily altered ion homeostasis (4). This is purported to reduce the mobility of tissue water molecules and leads to subsequent decrease in ADC (13,14).The apparent non-specificity of T 2 changes in DT2 data (Fig.…”

“…increased tissue oxygenation and perfusion) has previously been exploited using T Ã 2 -weighted MRI (12)(13)(14), and perfusion imaging (15) in rodent and feline models. Likewise, the profound cellular changes induced by SD have been the target of diffusionweighted MRI sequences, which allowed detection of transient cell swelling (16)(17)(18)(19)(20)(21).…”

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

“…This was later confirmed in rats using diffusion MR imaging (Beaulieu et al, 2000). These studies were restricted to the initial hours after the hemorrhage.…”

Characterization of Intrinsic Optical Signal during Spreading Depolarization

“…They have excellent temporal resolution, but recordings are only made on special locations. Also, magnetic resonance imaging (MRI) is used to record SD in several studies [13,14]. MRI is capable of collecting three-dimensional spatial information at different timepoints, but spatial resolution is only millimeter.…”