Police responded to the campus on Cedros Avenue just before 11 a.m. where 11 students were involved in a brawl in the school's courtyard area, school officials said.
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The two students stabbed are 16 and 15 years old. Two other teens were also injured but they weren't stabbed and their injuries were listed as non-life threatening.
According to Los Angeles Unified School District Superintendent Alberto Carvalho, three students were detained following the fight though further details weren't immediately disclosed.
The school was placed on a temporary lockdown as officers searched the campus. No other injuries were reported.
During an afternoon news conference, Carvalho said it will now allow LAUSD schools to request the presence of a school police officer on campus. That option was available before Wednesday's incident.
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"As of today, Van Nuys will have the presence of an officer within its school facilitates," he said.
The incident remains under investigation.
Anyone with information is urged to contact school police.