MAP2K4 and brain ischemia: For the first time, specific inhibition of MKK7 was sufficient to prevent excitotoxicity in vitro as well as cerebral ischemia in two different in vivo models.2, 4, 39 This confirms that excitotoxicity/cerebral ischemia leads to activation of MKK7/JNK pathway, without activating MKK4/JNK.