MMP-2 and/or MMP-9 are upregulated by microglia in disorders where PNN breakdown occurs, such as stroke [248, 249], multiple sclerosis [250, 251], and glioma [252, 253], and pharmacological MMP blockade in glioma ameliorates enhanced MMP-2/9 activity and associated PNN loss [160]. Here, MMP2 is linked to multiple sclerosis.