Brett Favre had a 20-year career in the NFL, including an iron-man stint in which he played in 321 straight games. But it was his last play in the league that was a painful exclamation point on his illustrious tenure. In December 2010, while playing for the Vikings, the quarterback was sacked and knocked out cold for about 10 to 15 seconds, suffering a concussion.

The impact of that crushing blow — the 525th sack of his career — continues to loom large for Favre as the issue of football-fueled brain injuries casts a shadow over the sport.

“There was a quarterback, Chris Miller, who had to carry his name and address and phone number in his back pocket. If he got lost, he’d pull out the paper. I always thought, ‘Gee, that’s bad, but it’s isolated,’” Favre, 48, tells The Post. “But each and every day, there’s more and more news that doesn’t bode well for me or the next guy.”

In recent years, Favre has noticed he’s become more forgetful. And he wonders if his occasional memory lapses are the result of encroaching old age or the beginning of irreversible brain damage brought on by years of play.

“One thing that stands out is forgetting simple words,” Favre says, “and struggling for what I can see but can’t place.”

It’s why the former Packers great has invested both his money and influence in a new concussion drug from Florida-based pharmaceutical company Prevacus.

Right now, the only prescription for a concussion is to simply rest. But a potentially groundbreaking drug, formally PRV-002 but commonly referred to as Prevacus, could change that.

Prevacus is being developed by neuroscientist Jacob VanLandingham, Ph.D., who works in the department of biomedical sciences at Florida State University. Favre met him about four years ago through a doctor friend and liked what he heard.

“It is simple,” Favre says of VanLandingham’s drug.

According to VanLandingham, Prevacus is taken nasally within minutes of an initial head trauma. Once absorbed into the brain, the drug is said to trigger three different positive reactions — the reduction of inflammation, swelling and stress — at the cellular level. In rats, it’s been shown to improve short-term memory and motor performance, as well as reduce depression and anxiety.

Patients would take the drug twice a day for 14 days to minimize the development of post-concussion symptoms, which include dizziness, short-term memory loss, chronic headaches and sleep disorders.

“By definition, it should reduce post traumatic stress disorder and post-concussion symptoms. In theory, we may find down the road it reduces chronic traumatic encephalopathy,” says VanLandingham, referring to the degenerative brain disease that has rocked the football world in recent years. (A blockbuster study out of Boston University last year found that 110 out of 111 deceased NFL football players had CTE, which can only be diagnosed posthumously.)

Favre has invested about half a million dollars of his own money and raised an additional $800,000 for Prevacus. He’s enlisted former gridiron warriors Kurt Warner, Matt Hasselbeck and Steve Mariucci for the company’s advisory board. He’s also lobbied the likes of NFL Chief Medical Officer Dr. Allen Sills and other powerful voices in the league, including Tom Brady.

“I just approached [Brady] in the off-season and told him what we had. He said, ‘Have Jake send some. I’ll try it on the sidelines,’” says Favre.

But the drug has a lot more hurdles to clear before the Patriots’ quarterback is seen inhaling a dose on the field of Gillette Stadium.

Clinical trials on humans are expected to begin this summer. If the drug is proven to be both safe and effective and gains FDA approval, Prevacus hopes to be on the market in three to four years.

But despite the initial excitement, experts caution that it may not be a magic bullet.

‘I’m scared to death about what my brain is going to be doing when I’m 60.’

“It could be a game changer, but until I see data behind it, I’m going to remain skeptical,” says Dr. Erin Manning, a neurologist at Manhattan’s Hospital for Special Surgery.

“It’s hard for me to get excited about something that hasn’t gone through the first round of human trials,” she adds. “There have been a lot of drugs that look promising in animal studies but, when it reached more extensive studies in humans, failed.”

Another barrier: Little is still known about what happens to the brain during a concussion.

“Ten years ago, concussions weren’t something people were looking into,” says Manning, who notes that’s finally changing.

And high-profile sports players are leading the charge. There is at least one other concussion drug in development called Oxeia, a synthetic gut hormone thought to improve memory. Seahawks cornerback Richard Sherman sits on its board.

But the potential impact of finding a drug that could mitigate — or even prevent — the neurological damage associated with concussions goes well beyond football players, including those injured in military combat, motor-vehicle accidents and other sports such as baseball and soccer.

Retired soccer legend Abby Wambach has suffered at least one concussion and plans to donate her brain to science when she dies. In March, a study out of Northwestern University found that women’s soccer — with its headers and hard collisions — had the highest per capita rate of concussions out of any sport.

“We all agree there is a problem,” Wambach, 37, tells The Post. “I don’t see why we’re not spending more money and time to treat the problem. I’m scared to death about what my brain is going to be doing when I’m 60.”

Former Chicago Cubs catcher David Ross — who retired from the MLB in 2016 — is a high-school friend of VanLandingham. Having suffered at least five concussions throughout his career, the 40-year-old is acutely aware of what the trauma has done to his brain and his lifestyle.

The two-time World Series champion says he can become overwhelmed in crowded, noisy spaces and has noticed mood swings. He jumped on the Prevacus train immediately. (Both Ross and Wambach have minor investments in the company and sit on the advisory board.)

“Baseball players worry [about CTE]. It’s not like football, where they care constantly having trouble down the road, but the bigger and stronger the athletes are, the faster the ball is being thrown and the harder the ball is being hit. It’s becoming a bigger problem.”

The father of three hears parents worry about allowing their kids to play sports and wants to make athletics safe for future generations.

“Here’s the scary part for me: when you have people stopping playing a sport that we all love. Baseball has provided for me, not just financially, but who I am as a person. It taught me to overcome adversity, deal with successes and failures. That creates character. That’s why we involve our kids in youth sports.”

Regardless of whether Prevacus becomes the white knight its creators hope, the process has lit a fire in Wambach.

“Solving this problem is going to be a consistent responsibility,” she says. “I don’t believe this has the opportunity to fail.”