Glutamate as a Marker of Infarct Growth in Acute Ischemic Stroke

REVIEW ARTICLE


Mar Castellanos ¹ and Antoni Dávalos ²

Affiliations: ¹Department of Neurology, Institut d’Investigacio´ Biome`dica de Girona, Hospital Universitari Doctor Josep Trueta, Girona, Spain and <sup>2</sup>Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Universidad Auto`noma de Barcelona, Badalona, Spain

ABSTRACT

Background
It has been demonstrated that glutamate plays a role as a biochemical mediator of cerebral ischemia. Here, we review the main clinical data regarding the association of glutamate and the clinical and radiological outcome of patients with acute ischemic stroke.

Methods
Studies included in this review mainly analyzed data from hemispheric infarctions within 12 h of symptom onset and evaluated by diffusion‐ and perfusion‐weighted imaging (DWI and PWI) at admission and 72 h of evolution, and glutamate levels analyzed at admission. Lesion enlargement was calculated as the absolute difference between the two DWI lesion volumes. The effect of glutamate levels on lesion growth was also evaluated in the four different neuroimaging profiles as per the DWI and PWI findings presented at admission.

Results
A high correlation is reported between glutamate and DWI lesion growth (Spearman correlation = 0.709; P<0.001), which is even higher when the lesion enlargement surpasses the volume of the area identified as penumbra (peripenumbral infarction) in the initial neuroimaging study (Spearman correlation = 0.803; P<0.001). After adjusting for confounders, glutamate is the most powerful predicting variable of lesion enlargement, even after introducing the penumbral volume into the model (β = 0.21; SD = 0.07; P = 0.004). With regard to the neuroimaging profile at admission, the association between glutamate and lesion growth remained significant only in patients with mismatch.

Conclusions
The data presented demonstrate that glutamate mediates lesion growth in patients with ischemic stroke, especially when there is still tissue at risk of infarction.

Keywords: ischemic stroke, penumbra, glutamate, spreading cortical depression, magnetic resonance imagining (MRI), diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI)
Correspondence: Mar Castellanos, Department of Neurology, Hospital Universitari Doctor Josep Trueta, Neurovascular Unit, Avda. Francia s/n, E-17007 Girona, Spain. Tel: (34)-972-940262; Fax: (34)-972-228296; e-mail: mcastellanos.girona.ics@gencat.cat,
mcastellanosr@medynet.com